asco 2022 oral presentation

ASCO Connection

The professional networking site for asco's worldwide oncology community, search form, 2022 asco annual meeting preview: advancing equitable cancer care through innovation.

Apr 28, 2022

As the premier global event in oncology, join us—in person or online—for innovative findings in cancer care

By Melanie Farrell, ASCO Communications

The ASCO Annual Meeting provides a forum to learn about and discuss the important issues and ongoing controversies in cancer care across a variety of disease sites, treatment approaches, and disciplines. Join more than 40,000 oncology professionals from around the world to stay up to date on new clinical cancer advances in every area of cancer research, gain real-time insights from world-renowned faculty, and connect with one of the largest, most diverse audiences in global oncology—in person or online.

The theme for this year’s meeting, selected by 2021–2022 ASCO president Everett E. Vokes, MD, FASCO, encourages attendees to learn firsthand about some of the most recent innovations in oncology that will undoubtedly contribute to a future of more equitable cancer care. “Advancing Equitable Cancer Care Through Innovation” signifies the need to uncover fresh solutions that fundamentally improve the lives of all those touched by cancer, leading us toward a future of equity in cancer care.

“In oncology, innovation can be seen around every corner. Opportunities range from new therapies and smarter use of existing treatments, and offering patients broader and easier access through telemedicine, to rethinking clinical trial eligibility and much more. As a global community of innovators, people working in oncology have unmatched potential to improve care for all patients, everywhere in the world,” Dr. Vokes said.

Attendees will see the theme reflected in sessions throughout the meeting, and during Dr. Vokes’ Presidential Address at the Opening Session .

“This is our time to gather, and exchange novel ideas that can bring down barriers to access and make cancer care more equitable, convenient, and efficient for patients worldwide,” Dr. Vokes said.

ASCO is honored that so many oncology professionals will be attending the 2022 Annual Meeting. Read on for highlights of the can’t-miss events, tips for connecting with colleagues, and new features for 2022 to personalize your meeting experience and make the most of every session you attend.

Program information in this story is current as of March 21, 2022. Visit meetings.asco.org for the most current information on the 2022 ASCO Annual Meeting.  ​ Conquer Cancer, the ASCO Foundation, is proud to support the 2022 ASCO Annual Meeting. Visit CONQUER.org to find out how you can support innovative research for every cancer, every patient, everywhere.

2022 Program Highlights

Whether attendees are participating in ASCO22 in person or remotely, they will find a robust, unified digital experience at meetings.asco.org . The URL is accessible on any device’s web browser, without the need to download a separate app. Through meetings.asco.org , attendees can:

• Review the most up-to-date program, build a personal schedule of sessions, and export the schedule to their preferred calendar
• Watch over 85 livestream sessions, including Opening Session, Plenary Session, many Special Sessions, and all Oral Abstract Sessions
• Engage with the meeting using point-of-session-based tools, including Q&A, case-based polling, and note-taking on slides
• Connect with other attendees using direct private messages through the Find a Colleague directory
• View or rewatch most sessions on-demand after they’ve concluded
• View or download over 2,000 posters
• Access materials from the session, including abstracts, slides, and transcripts
• Claim CME for participation in each session

Opening Session

On Saturday, June 4, in Hall B1, ASCO will kick off the meeting with its Opening Session , which will include the Guest Speaker’s Address, Presidential Address, and David A. Karnofsky Memorial Award and Lecture. In this year’s Opening Session, Dr. Vokes will deliver the presidential address on his theme and its message: how to advance equitable cancer care through innovation. (Following the presentation, the full transcript and video of the address will be available on ASCO Connection .)

ASCO is delighted to welcome André Ilbawi, MD, as the session’s keynote speaker. Dr. Ilbawi is a double-board certified surgical oncologist responsible for the development of the World Health Organization (WHO)/International Agency for Research on Cancer (IARC) priority setting tool for cancer control. He led and supported the launches of the WHO Global Initiative for Childhood Cancer and the WHO Global Breast Cancer Initiative, in addition to implementing the WHO Cervical Cancer Initiative. Dr. Ilbawi is the WHO technical lead in the Global Platform for Access to Childhood Cancer Medicines, which seeks to universally provide cancer medicines for all children in resource-challenged countries.

Attendees will also hear from David A. Karnofsky Memorial Award recipient Jedd Wolchok, MD, PhD, FASCO, who is being recognized for his pioneering work in immunotherapy. The most recent recipients of the Fellow of the American Society of Clinical Oncology (FASCO) honor will be recognized for their service to the Society. ( Read more about Dr. Wolchok, FASCO honorees, and other recipients of 2022 Special Awards .) Opening Session speakers will also include Conquer Cancer Board chair Howard A. Burris III, MD, FACP, FASCO.

Science Program

This year, over 6,000 abstracts were submitted for consideration by the Annual Meeting Scientific Program Committee. More than 2,900 abstracts were selected for presentation in Oral Abstract Sessions, Clinical Science Symposia, and Poster Sessions, plus more than 2,200 for online publication. The majority of abstracts will be released on May 26, 2022, at 5 PM (ET) on asco.org/abstracts . Late-Breaking Abstracts (LBAs) will be released on a rolling basis during the meeting.

“The ASCO Annual Meeting is the premier place to present the most impactful data when it comes to taking care of patients with cancer. The size, reach, and quality of presentations is outstanding,” said 2022 Annual Meeting Scientific Program Committee chair Sonali Smith, MD. “It is not only the venue for presenting the latest clinical advances, but also the glue for our oncology community.”

Plenary Session

The Plenary Session showcases abstract presentations of the top practice-changing science, with commentary from expert discussants. This is the must-see session of the meeting, highlighting the most clinically relevant science that will change current cancer care. Plan to join the live Plenary Session presentation on Sunday, June 5, at 1 PM (CT) and participate in Q&A with the speakers and discussants.

ASCO Plenary Series

Combining the immediacy of the online world with the scientific rigor and practice-changing data of ASCO’s live meetings, the ASCO Plenary Series session brings tomorrow’s practice-changing science to clinicians today. Research presented throughout the 2021–2022 virtual Plenary Series will be showcased during a special session at the ASCO Annual Meeting. Be sure to attend ASCO Plenary Series: Rapid Abstract Updates on Sunday, June 5, at 4:30 PM (CT). Visit plenaryseries.asco.org to see Plenary Series dates for the fall.

Clinical Science Symposia

Clinical Science Symposia are designed to address a cross-cutting theme or hot topic in oncology while integrating abstracts with expert discussion. The following Clinical Science Symposia have been planned this year:

• ctDNA: Dawn of a New Era
• Bispecifics: Is Two Better Than One?
• Is There a Ghost in the Machine? Putting Artificial Intelligence to Work
• Including the Excluded: Advancing Care for All Patients With Lung Cancer
• Beating Bad Blood: The Power of Immunotherapy in Hematologic Malignancies
• Aspirations of Equity in Oncology
• Looking Everywhere for Determinants of Benefit From Immunotherapy
• Can We Begin to Predict Responders to Targeted Therapy in GI Cancer?
• Biomarkers Beyond Histology in Contemporary Sarcoma Clinical Trials
• The Dr. Bernard Fisher Memorial Annual Clinical Science Symposium Supported by the Breast Cancer Research Foundation: Utility of Genomics to Guide Treatments in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer
• Expanding the Reach of Genetic Testing
• Molecular-Based Treatment for Endometrial Cancer
• Moving Past Geriatric Assessments to Implementation

Education Program

The Annual Meeting Education Program offers a robust portfolio of sessions that address the concerns and priorities of everyone in the cancer care space. These sessions are designed to teach and engage participants across disciplines, as well as impart practical, take-home knowledge that can be applied to any cancer care setting.

When curating the 2022 Education Program, the Annual Meeting Education Committee was inspired by the meeting’s theme to look at global cancer care through the lens of equity and innovation.

“I am excited about sharing and hearing the latest advances in our field, so we can move toward impact, innovation, and equity across our global cancer community. Whether attendees join us in person or online for the ASCO Annual Meeting, we are all coming together for a common goal of reducing the cancer burden,” said 2022 Annual Meeting Education Committee chair Jhanelle Gray, MD.

Sessions of particular interest this year include:

• Cancer Groundshot: Addressing the Global and National Inequities in Cancer Care
• New Drugs in Oncology: Incorporation Into Practice
• Strategies to Advance Equity in Cancer Clinical Trials
• COVID-19 and Cancer: Advantages and Disadvantages of Immunotherapy
• Rethinking Cancer Clinical Trial Conduct With Telemedicine
• Depersonalized Medicine: Who Is Missing in Big Data?
• Artificial Intelligence in Oncology: The Current Field and Where It Is Headed

Case-Based Panel Sessions

Case-Based Panel Sessions will feature expert faculty discussing timely and challenging real-world clinical scenarios. These sessions will be highly interactive, offering both Q&A and participant polling. Along with disease-specific case-based scenarios, Case-Based Panel Session highlights include:

• Ethical Dilemmas Among Genetic Testing
• Practical Use of Geriatric Assessment Tools for Older Adults With Cancer: Can Technology Take Us Further?
• Strategies to Address Moral Distress in Clinicians: What Should We Do When We Don’t Know What to Do?
• Less Is More: Practical De-Implementation Science Strategies to Improve Quality
• Burnout and Mental Health in Oncology Providers: You Are Not Alone
• Immune Checkpoint Inhibitors: Long-Term Survival Data
• Pharmacogenetic Testing to Personalize Cancer Therapy: Ready or Not?
• Loneliness: A Forgotten Challenge in Cancer Care

Joint Sessions

At the Annual Meeting, ASCO partners with likeminded organizations to host joint sessions on pertinent topics in oncology. Two joint sessions will be offered this year:

• ASCO/European Cancer Organisation Joint Session: HPV Vaccination, Prevention, and Treatment
• ASCO/American Association for Cancer Research (AACR) Joint Session: The Promise of DNA Damage Response and Repair in Cancer

Sharing Our Stories

ASCO Voices

ASCO Voices continues to be one of the most compelling sessions offered at the ASCO Annual Meeting, featuring personal stories from across the oncology continuum. This year’s session will showcase stories focused on a topic relevant to issues of equity, global health, and innovation. The following speakers were selected to share their passions, stories, and perspectives—without notes or slides:

• “Cancer: Common Humanity, Different Worlds” by Kevin Diasti, MD
• “The 5AM Wake-up Call” by Omar Abdihamid, MMed
• “Bridging the Gap Between Clinical Care and Clinical Research By Improving Access to Clinical Trials With Technology” by Neal Meropol, MD, FASCO
• “Moving Online, Together!” by Khamai Simpson, MSc
• “Equity in Clinical Trial Access: We Should Not Need Physician Friends” by Louise Brennan, PhD

Film Screening

Attendees are invited to attend a screening of Can You Hear My Voice? , a documentary film about London’s Shout at Cancer Choir , whose singers are living without voice boxes. The film will be screened in the McCormick Place Lakeside Lounge on Saturday, June 4, from 5:00 PM-6:30 PM (CT).

The film was produced and directed by Bill Brummel, who had his own voice box removed in 2016. Mr. Brummel is an award-winning documentary producer/director. He and his films have been recognized with a Peabody Award, two International Documentary Association (IDA) Awards, five national Emmy nominations, and been named to an Oscar shortlist.

On Monday, June 6, Mr. Brummel and the surgeon who treated him will participate in a discussion for ASCO’s Oncology, Etc. podcast . Attendees are welcome to join from 3:00 PM-4:00 PM (CT) in Room S100a.

Make the Most of Your In-Person Experience

After 2 years of joining the ASCO Annual Meeting from your home or office, it’s time to step out from behind those webcams, dust off your business attire, and put on your most comfortable shoes because we are ready and excited to welcome attendees back in person in Chicago.

Health and Safety at ASCO22

We are continuously evolving our protocols to ensure the safety of our attendees. Visit the Health and Safety webpage for the most current information, including:

• Vaccination Requirements:   All in-person attendees at the ASCO Annual Meeting must be fully vaccinated against COVID-19 by the time of the meeting. “Fully vaccinated” means either 2 weeks have passed since receiving the second dose of an FDA- or WHO-authorized double-dose COVID-19 vaccine or 2 weeks have passed since receiving the one dose of an FDA- or WHO-authorized single-dose COVID-19 vaccine. Please note that your registration is not complete until you verify your vaccination.
• Travel From Outside the United States:  The Health and Safety webpage will provide the latest country-specific COVID-19 requirements, as well as COVID-19 protocols at Chicago’s O’Hare International Airport and Midway International Airport.
• COVID-19 Testing:   Free COVID-19 testing will be available for registered attendees who experience symptoms onsite and for registered attendees who must show proof of a recent negative COVID-19 test to board their return flight.
• Masks:   We are following CDC, state, and local guidelines regarding masking. Please refer to the Health and Safety webpage prior to attending the meeting for the most current information about masking.

Ticketed Sessions

Ticketed Sessions (purchase required) will be available in-person only, and will not be recorded for on-demand viewing. Participate in intimate discussions with expert faculty on 22 focused topics, including:

• Meet the Professors: Emerging Screening Options for Early Cancer Detection
• Point/Counterpoint: Real-World Data—Do We Even Need Clinical Trials Anymore?
• Meet the Professors: Editors’ Insights on How to Successfully Publish in Top Oncology Journals Internationally
• Clinical Controversies: Management of Pleural Mesothelioma in the Era of Immunotherapy

Grow Your Professional Network

Along with exciting new scientific presentations and world-class educational programming, a significant benefit of attending the ASCO Annual Meeting is making face-to-face connections with some of the best and brightest in oncology. There are many opportunities to meet your next research collaborator, co-author, mentor, mentee, hiring manager, or new friend. Here are some ways to make connections that will generate future collaborative research ideas:

• Women’s Networking Center: Connect with other women in oncology and sign up for individual mentoring sessions.
• Publishing Lounge: Meet the editors-in-chief and catch up on the latest practice-changing research in global oncology.
• Trainee & Early-Career Oncologist Member Lounge: Seek career advice and network with peers and experienced professionals in the field.
• Patient Advocate Lounge: Connect and share stories in a relaxed environment, and take advantage of patient information materials.
• Lakeside Lounge: Relax, recharge, grab a bite to eat, and connect with colleagues.
• ASCO Central: Meet face-to-face with ASCO staff to learn more about the programs and services ASCO has to offer, the resources available to you, and how to get involved.
• Networking Tables: Reserve a table in advance so you know when and where to meet with colleagues.
• Career Fair: Explore available career options and meet face-to-face with recruiters in the field of oncology. The career fair will be located in the back of the Exhibit Hall (Hall A).
• Southside Library: Located near Gate 2 in the South Building, Level 1, the Southside Library offers a quiet setting to network, charge devices, and grab a coffee or quick bite to eat, while reading available ASCO publications.

Onsite Amenities and Support

Free Onsite Childcare: Available for children ages 6 months to 12 years on a first-come, first-served basis. ASCO welcomes working parents and their children at the meeting. Check availability, review Health and Safety policies, and learn more .

Additional amenities and support include :

• Nursing Room
• Prayer Room
• Quiet Spaces
• Charging Stations
• Hotel and Chicago Concierge Desk
• CE and Technical Assistance HelpDesk
• ASCO Membership Information
• Multilingual Interpreters
• ASCO Store Digital Products and Merchandise

Transportation

There are multiple transportation options to help you reach ASCO22:

• Complimentary shuttle service: Available to and from all official ASCO hotels and McCormick Place, except those within walking distance.
• Metra (commuter train system) and CTA (the “L” light rail system):  Metra station is located in McCormick Place, with free Metra tickets available for attendees to Randolph Street Millennium Station (the heart of downtown Chicago).
• Taxi and ridesharing: Designated pickup/drop off locations are located throughout McCormick Place.
• Bike sharing (Divvy): Make transportation your exercise for the day.

Experience ASCO22 Online

Just as the COVID-19 pandemic led to innovative new approaches using telehealth and telemedicine, ASCO has been innovative when it comes to providing access to the groundbreaking science in oncology, the latest trends in clinical application, and treatment and insights on equitable cancer care that the 2022 ASCO Annual Meeting has to offer.

That is why ASCO is providing a robust online meeting experience to help break down other barriers that may prevent members of the global oncology community from getting this needed information, whether it be travel restrictions, budget constraints, clinic schedules, family obligations, or health concerns. Visit meetings.asco.org to find everything you need to participate in ASCO22 remotely.

Follow the 2022 ASCO Annual Meeting on Social Media

Connect with ASCO on social media to keep up with the latest information from the 2022 ASCO Annual Meeting. Follow along on Twitter ( @ASCO ) and Instagram ( @ascocancer ) and share your own meeting experience using the hashtag #ASCO22 . You can also follow ASCO volunteers who have committed to leading a robust conversation throughout the meeting on Twitter and Instagram.

You don’t want to miss the lively and substantive conversation—ASCO21 Virtual generated significant social media engagement: 8,900 Twitter users sent 55,296 tweets using the 2021 meeting hashtag, with approximately 461 tweets an hour.

ASCO Daily News : Your Daily Conference Reporter and More

Catch up on key sessions and clinical takeaways with high-quality, unbiased research summaries and oncology news. ASCO Daily News content is available online all year. Subscribe to ASCO Daily News emails for up-to-the-minute coverage before, during, and after the meeting. To opt-in to ASCO Daily News communications, select “ASCO Journals Updates and Oncology News” in your email preference center .

ASCO members and meeting participants will receive the print ASCO Daily News: ASCO Annual Meeting Wrap Up issue, highlighting the most practice-changing science presented, several weeks after the meeting concludes.

Prefer to listen rather than read? The ASCO Daily News Podcast highlights key abstracts and research summaries from experts in the field. 

2022 ASCO Educational Book

Articles in the ASCO Educational Book are authored by the ASCO Annual Meeting Education Program faculty and other invited experts. Topics cover the most compelling research and newest standards of care in the field, with the goal of improving patient care and value. Each year, the best minds in oncology come together to author scholarly reviews for the PubMed-indexed ASCO Educational Book . Catch up on the newest developments in the multidisciplinary fields of oncology. Articles are free to read and download . Please note that the 2022 edition is available online-only.

Are You Ready for ASCO22?

The 2022 ASCO Annual Meeting is just a few weeks away, but you still have time to prepare.

May 2022: 1 month out

• Look over preliminary Annual Meeting materials at meetings.asco.org .
• Ensure that you have verified your COVID-19 vaccination status as part of your registration: your registration is not complete until you do! Review the latest health and safety protocols .
• Once you’ve registered, use the Find a Colleague directory on meetings.asco.org to find others who have registered and send them a private direct message.
• May 26 at 5 PM (ET): View the majority of the 2022 abstracts on asco.org/abstracts .
• If you haven’t already, set up your account on Twitter and Instagram and download their apps. Find us @ASCO on Twitter and @ascocancer on Instagram; share your thoughts with the hashtag #ASCO22 on both platforms.

Week of May 27: 1 week out

• Test your login, test your login, test your login! Whether you are attending in person or virtually, make sure you are ready to access sessions by testing your login on meetings.asco.org . ASCO staff are standing by to help you with any login questions. The earlier you realize you need help, the smoother your meeting experience will be.
• Read ASCO Daily News online for session preview articles and insights from renowned experts in the field.
• Check out the 2022 ASCO Educational Book for articles written by Education Program faculty.
• Visit meetings.asco.org to scroll through all the ASCO22 sessions, and save sessions you want to attend to help plan your schedule.

June 3 through June 7: 2022 ASCO Annual Meeting

• Read ASCO Daily News for session coverage and more.
• Use meetings.asco.org for point-of-session–based tools like polling, Q&A, note-taking, and to claim CME.
• Start your meeting with a refreshing beverage—join ASCO leadership at the McCormick Place main entrance on Friday, June 3, at 1 PM (CT), as they hand out glasses of lemonade.
• Need a new headshot? Free professional headshots are available on Friday, June 3, through Monday, June 6, from 10 AM to 5 PM (CT) near Starbucks by Concierge Services.
• Engage in live Q&A with faculty during in-person and livestreamed sessions.
• Participate in the #ASCOiSpy scavenger hunt on Twitter.
• Explore the Exhibits in the Exhibit Hall and participate in an Industry Expert Theater session.
• Carve out time on Saturday, June 4, and Sunday, June 5, from 11 AM to 3 PM (CT), to visit ASCO Central and meet some lovable dogs who want nothing more than to help you unwind.
• Search the Pharmaceutical Pipelines and Clinical Trials Directories for current information on pharmaceuticals in development and ongoing clinical trials.
• Show your ASCO pride: ASCO merchandise is available for purchase at the ASCO Store and online.

After the Annual Meeting:

• Watch on-demand videos of sessions you missed or want to review again.
• Share what you learned with your colleagues and patients.
• Access Meeting Videos and Slides on meetinglibrary.asco.org , an online library of abstracts, slides, posters, and recorded presentations from most sessions. Access is included in your meeting registration.
• Submit your Meeting Feedback Form. Tell us how we can make the 2023 ASCO Annual Meeting even more valuable for you.
• Mark your calendar for the 2023 ASCO Annual Meeting: June 2–6, 2023, in Chicago, IL!

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ASCO 2022 - Meeting Highlights PPT Presentation

This one-hour live session will synthesize lung cancer research presented at the June 3-7 live meeting of the American Society of Clinical Oncology (ASCO). It will address physicians' need to keep abreast of current research and future trends to inform clinical practice.

Format: Dr. Antoinette Wozniak will moderate the program and lead the discussion and question and answer session following presentations by Shirish M. Gadgeel, MD and Karen Reckamp, MD, MS. Dr. Gadgeel will review Targeted Therapies, Dr. Reckamp will discuss Immunotherapy topics

The content on this site is intended for healthcare professionals only

• Conferences

ASCO 2022: Head and neck cancer highlights

Please rate this video, the information in this video was of interest to me, the information in this video is likely to improve my clinical practice or research, i would recommend this video to my colleagues.

Dr Mark Persky speaks to ecancer about the highlights from ASCO 2022 in the field of head and neck cancer. Dr Persky initially talks about immunotherapy for head and neck tumours and explains what immunotherapy entails.

Dr Persky then discusses checkpoint inhibitors and explains their mechanism of action. He says PDL-1 detection is important in deciding what treatment to give to patients and PDL-1 targeted therapies are very effective. 

He mentions the recent use of circulating tumour DNA; detection of occult tumour DNA among patients treated for HPV-driven oropharyngeal squamous cell carcinoma patients. 

Dr Persky mentions that oropharyngeal cancers happen mostly because of HPV. He discusses the role of ctDNA post-operation and for diagnostics. This can also determine the progress of the treatment.

Dr Persky discusses the phase II findings on pembrolizumab and cabozantinib from ASCO 2022  by Neil Saba.

• Categories:
• Head & neck
• Personalised medicine
• Organisation of cancer
• Control, survivorships & outcomes
• Antibodies & immunotherapy
• Cell therapy & stem cells
• Drug development
• Targeted molecules

It’s my pleasure to be invited to talk about some of the recent advances in the treatment of head and neck cancer. I basically want to concentrate on three that I think have really come to the forefront in incredible ways of changes in the way we do handle head and neck cancer. The most appealing one and the most active one at this point, where much research is going on, is the immunotherapy of head and neck cancer tumours. It’s not only head and neck cancer tumours but other tumours too that are involved with this but obviously my area of expertise is with the head and neck cancer tumours. We’re talking about not chemotherapy, not anything that directly damages or attacks the tumour cells, but what enhances the immune system to recognise the tumour cells and for them to do the actual activity in destroying the tumour cells. 

The most frequent mechanism for that is something called checkpoint inhibitors where the medication that we administer allows the immune cells of the body to recognise the tumour cells and to destroy them in a very, very effective way. One way of performing that and to find out if this tumour is indeed sensitive to this type of checkpoint inhibitor is to test the tumour cells for something called PD-L1 which is the pathway by which the tumour cell tries to turn off the recognition of the immune cell from recognising it as a tumour and thereby protecting itself. But this interferes with that pathway and the PD-L1 pathway is the checkpoint inhibitor pathway and it’s something that has been incredibly effective in tumours that demonstrate indeed they do contain PD-L1 and we actually get something called the CPS score to find out what percentage of the tumour cells are sensitive to this route. The higher the number of cells as far as percentage-wise, the more effective this type of therapy is.

We’ve been performing that for more advanced tumour stages and we’ve been seeing remarkable results in those tumours that demonstrate PD-L1 activity. The main drug that we use is something called pembrolizumab and that’s very effective in our hands in addressing these particular tumours. Recent research that is going on with this shows more and more that this has been an effective route to treat these tumours.  We can talk about it a bit more if we have any additional questions but there’s again significant research. 

Another area that has been incredibly active and very helpful for us is performing… Many of the tumours that occur at this point, especially in the area of the oropharynx, the oropharynx being the palatine tonsils, the lingual tonsils at the base of the tongue and also the rest of the oropharynx and the base of the tongue and the back of the throat. Many of these tumours, more and more, are not being caused as frequently by smoking and drinking exposure, smoking and alcohol exposure, but by HPV, human papilloma virus, exposure. 

We have discovered more recently, in the past year or so, and again additional research is going on with this, that we can actually measure something called the ctDNA which is the circulating tumour DNA, the DNA that comes from the HPV that is causing this tumour. We can evaluate the titres of that in the bloodstream before treatment and can follow the progress, hopefully the positive progress, that our treatment plan has against decreasing the titres of these ctDNA, of the circulating tumour DNA. So if we obtain these titres before treatment and actually perform these titres either postoperatively, after an operation, to determine if there is eradication of that type of DNA, or as we treat them with either immunotherapy or chemotherapy or radiation, we can determine the progress in our treatment and the elimination of the tumour cells by following the titres in these tumour patients.

So these are two areas that really a lot of research has been performed and will continue to be done and we find very promising. For instance, with the HPV ctDNA, the circulating tumour DNA, if we perform a surgery on them, and nowadays there are a certain amount of patients who can fall into the realm of undergoing transoral robotic surgery for this, which is a less invasive way of handling these tumours if they are at the proper stage, the comparison of the preoperative ctDNA to the postoperative ctDNA really gives us an effective method of knowing if the entire tumour has been removed, both from the primary site and also from any of the potential lymph nodes that may be involved with metastatic disease in the neck too. So often the ctDNA will go down to zero immediately after the operation which obviously portends an excellent result from the operation. 

We have been following these patients, again this is relatively short-term follow-up because this hasn’t been noted until most recently, but we also noticed that if there’s an increase in the ctDNA that one must be very concerned about the recurrence of tumour that may not be as clinically evident as with our examinations or even some of our radiographic studies. So this too is what we think is a very sensitive way of determining recurrent tumour by doing this blood test.

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What can we help you find?

Merck to present data at 2022 asco annual meeting highlighting promising pipeline medicines and significant progress in treating earlier stages of certain cancers with keytruda® (pembrolizumab).

May 10, 2022 6:45 am ET

Data from studies of six medicines and pipeline candidates in more than 25 cancers to be presented

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that data for six approved medicines and pipeline candidates in more than 25 types of cancer will be presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from June 3-7. Presentations will feature new or updated findings from Merck’s broad portfolio of cancer medicines: KEYTRUDA; WELIREG™ (belzutifan); LYNPARZA ® (olaparib, in collaboration with AstraZeneca); and LENVIMA ® (lenvatinib, in collaboration with Eisai). Additionally, Merck will present data from its diverse pipeline of immuno-therapeutic candidates, including the investigational anti-LAG-3 therapy favezelimab and the investigational anti-ILT3 therapy MK-0482.

“The medicines in our broad portfolio have helped transform the treatment of many advanced cancers, but patients continue to need new treatment approaches and new medicines,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are delighted to share the progress we are making across our expansive and diverse oncology portfolio and pipeline, including in earlier stages of cancer and in some of the most common types of cancer such as melanoma, non-small cell lung cancer, renal cell carcinoma and triple-negative breast cancer.”

Key data from Merck’s portfolio to be presented at ASCO:

• First presentation of distant metastasis-free survival (DMFS) and updated recurrence-free survival findings from the Phase 3 KEYNOTE-716 trial evaluating KEYTRUDA as adjuvant therapy in resected stage IIB and IIC melanoma (Abstract #LBA9500). Earlier this year, Merck reported that KEYNOTE-716 met its key secondary endpoint of DMFS as adjuvant treatment for these patients. Additionally, health-related quality-of-life data for KEYNOTE-716 will be presented for the first time (Abstract #9581);
• Data from a subgroup analysis of the Phase 3 KEYNOTE-091 trial evaluating outcomes related to surgery, disease burden and adjuvant chemotherapy in patients with stage IB (greater than 4 cm) – stage III non-small cell lung cancer (NSCLC) treated with KEYTRUDA in the adjuvant setting following complete resection (Abstract #8512);
• Additional long-term efficacy analyses of the Phase 3 KEYNOTE-564 trial evaluating KEYTRUDA in the adjuvant setting for patients with renal cell carcinoma (RCC) who are at intermediate-high to high risk of recurrence following nephrectomy (Abstract #4512);
• Exploratory analysis of the Phase 3 KEYNOTE-426 trial evaluating KEYTRUDA plus axitinib as first-line therapy for advanced clear cell RCC following progression after first subsequent therapy (Abstract #4513);
• Exploratory analysis from the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA plus chemotherapy in the neoadjuvant setting in patients with early-stage triple-negative breast cancer investigating event-free survival by residual cancer burden (Abstract #502);
• Subgroup analysis from the Phase 3 KEYNOTE-826 trial evaluating KEYTRUDA plus chemotherapy as first-line treatment for patients with persistent, recurrent or metastatic cervical cancer (Abstract #5506);
• Three-year follow-up data from the Phase 1 LITESPARK-001 trial evaluating WELIREG from the advanced clear cell RCC cohort (Abstract #4509) and two-year follow-up data from the Phase 2 LITESPARK-004 trial evaluating WELIREG in von-Hippel-Lindau disease (Abstract #4546).

Key data from Merck’s pipeline to be presented at ASCO:

• First presentation of results from Cohort 1 of a Phase 1/2 study evaluating the anti-LAG-3 antibody, favezelimab plus KEYTRUDA in patients with anti-PD-1-naïve relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) (Abstract #7516). Results for Cohort 2 of this study evaluating favezelimab plus KEYTRUDA in patients with R/R cHL after anti-PD-1 treatment will also be presented for the first time (Abstract #7545).

For more information about our data presentations at ASCO and to learn more about Merck’s commitment to cancer research and patients, please visit https://www.merck.com/media/merck-at-asco-2022/ .

Merck investor event

Merck will host an Oncology Investor Event to coincide with the ASCO Annual Meeting on Tuesday, June 7, 2022, 7-8 a.m. CT, at which senior management will provide an update on the company’s oncology strategy and program. The event will take place in Chicago and will be accessible via webcast. Further details including the webcast link will be announced at a later date.

Details on abstracts listed above and additional key abstracts for Merck

Breast cancer

• Abstract #503, Oral Presentation: Event-Free Survival By Residual Cancer Burden After Neoadjuvant Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy For Early TNBC: Exploratory Analysis From KEYNOTE-522. L. Pusztai.

Gastrointestinal cancers

• Abstract #4109, Poster Presentation: Pembrolizumab Monotherapy For Previously Untreated Advanced Hepatocellular Carcinoma (aHCC): 3-Year Follow-Up Of The Phase 2 KEYNOTE-224 Study. I. Borbath;
• Abstract #4088, Poster Presentation: Health-Related Quality Of Life (HRQoL) Impact Of Pembrolizumab (Pembro) Plus Best Supportive Care (BSC) Versus Placebo (PBO) Plus BSC As Second-Line (2L) Therapy In Patients (Pts) In Asia With Advanced Hepatocellular Carcinoma (HCC): Phase 3 KEYNOTE-394 Study. S. Qin.

Genitourinary cancer

• Abstract #4561, Poster Presentation: Health-Related Quality Of Life (HRQoL) For Patients With Advanced/Metastatic Urothelial Carcinoma (UC) Enrolled In KEYNOTE-052 Who Are Potentially Platinum Ineligible. R. Morales-Barrera;
• Abstract #4513, Poster Discussion: Pembrolizumab (Pembro) Plus Axitinib (Axi) Versus Sunitinib As First-Line Therapy For Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Analysis Of Progression After First Subsequent Therapy In KEYNOTE-426. T. Powles;
• Abstract #4512, Poster Discussion: Adjuvant Pembrolizumab For Post-nephrectomy Renal Cell Carcinoma (RCC): Expanded Efficacy Analyses From KEYNOTE-564. T. Choueiri;
• Abstract #4509, Poster Discussion: Phase 1 LITESPARK-001 (MK-6482-001) Study Of Belzutifan In Advanced Solid Tumors: Update Of The Clear Cell Renal Cell Carcinoma (ccRCC) Cohort With More Than 3 Years Of Total Follow-Up. E. Jonasch;
• Abstract #4546, Poster Presentation: LITESPARK-004 (MK-6482-004) Phase 2 Study Of Belzutifan, An Oral Hypoxia-Inducible Factor 2α Inhibitor (HIF-2α), For Von Hippel-Lindau (VHL) Disease: Update With More Than Two Years Of Follow-Up Data. E. Jonasch;
• Abstract #4514, Poster Discussion: Impact Of Subsequent Therapies In Patients (Pts) With Advanced Renal Cell Carcinoma (aRCC) Receiving Lenvatinib Plus Pembrolizumab (LEN + PEMBRO) Or Sunitinib (SUN) In The CLEAR Study. M. Voss.

Gynecologic cancers

• Abstract #5506, Oral Presentation: Pembrolizumab + Chemotherapy In Patients With Persistent, Recurrent, Or Metastatic Cervical Cancer: Subgroup Analysis Of KEYNOTE-826. K.S. Tewari;
• Abstract #5560, Poster Presentation: Quality Of Life In Patients With Advanced High-Grade Ovarian Cancer (HGOC) Receiving Maintenance Therapies After First-Line (1L) Chemotherapy In The Randomized Phase III PAOLA-1/ENGOT-ov25 Trial (NCT02477644). J.E. Kurtz;
• Abstract #5571, Poster Presentation: Efficacy Of Maintenance Olaparib Plus Bevacizumab In Patients With Newly Diagnosed Advanced Ovarian Cancer According To BRCA Mutation Genotype In The Phase III PAOLA-1/ENGOT-ov25 Trial. S.I. Labidi-Galy;
• Abstract #5587, Poster Presentation: Efficacy Of Next Line Of Therapy After Treatment With Lenvatinib (LEN) In Combination With Pembrolizumab (Pembro) Versus Treatment Of Physician’s Choice (TPC) In Patients (Pts) With Advanced Endometrial Cancer (aEC): Exploratory Analysis Of Study 309/KEYNOTE-775. V. Makker.
• Abstract #7516, Poster Discussion: Favezelimab (Anti–LAG-3) Plus Pembrolizumab In Patients With Anti–PD-1–Naïve Relapsed Or Refractory (R/R) Classical Hodgkin Lymphoma (cHL): An Open-Label Phase 1/2 Study. N. Johnson;
• Abstract #7545, Poster Presentation: Favezelimab (Anti–LAG-3) Plus Pembrolizumab In Patients With Relapsed Or Refractory (R/R) Classical Hodgkin Lymphoma (cHL) After Anti –PD-1 Treatment: An Open-Label Phase 1/2 Study. J. Timmerman.

Lung cancer

• Abstract #8512, Poster Discussion: EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 Study Of Pembrolizumab Versus Placebo For Completely Resected Early-Stage Non-Small-Cell Lung Cancer (NSCLC): Outcomes In Subgroups Related To Surgery, Disease Burden, And Adjuvant Chemotherapy Use. M. O’Brien;
• Abstract #8508, Poster Discussion: Two-Year Update From KEYNOTE-799: Pembrolizumab Plus Concurrent Chemoradiation Therapy (cCRT) For Unresectable, Locally Advanced, Stage III NSCLC. M. Reck.
• Abstract #LBA9500, Oral Presentation: Distant Metastasis-Free Survival With Pembrolizumab Versus Placebo As Adjuvant Therapy In Stage IIB Or IIC Melanoma: The Phase 3 KEYNOTE-716 Study. G. Long;
• Abstract #9581, Poster Presentation: Health-Related Quality Of Life (HRQoL) With Pembrolizumab (Pembro) In Resected High-Risk Stage II Melanoma In The Phase 3 KEYNOTE-716 Study. M.A. Khattak.

Solid tumors

• Abstract #2505, Oral Presentation: Phase 1 First-In-Human Study Of Anti–ILT3 mAb MK-0482 As Monotherapy And In Combination With Pembrolizumab In Advanced Solid Tumors: Dose Escalation Results. M. Gutierrez.

About Merck’s early-stage cancer clinical program

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.

About KEYTRUDA ® (pembrolizumab) injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA ® (pembrolizumab) Indications in the U.S.

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

• stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
• metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.

KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

• who are not eligible for any platinum-containing chemotherapy, or
• who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Non-muscle Invasive Bladder Cancer

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

• in combination with platinum- and fluoropyrimidine-based chemotherapy, or
• as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Cervical Cancer

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA, in combination with LENVIMA, is indicated for the first-line treatment of adult patients with advanced RCC.

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma

KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System : Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular : Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal : Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue : Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine : Hypoparathyroidism; Hematologic/Immune : Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients with stage III melanoma, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054.

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-204, KEYTRUDA was discontinued due to adverse reactions in 14% of 148 patients with cHL. Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA; those ≥1% were pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three patients died from causes other than disease progression: 2 from complications after allogeneic HSCT and 1 from unknown cause. The most common adverse reactions (≥20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash, and cough (20% each).

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those ≥1% were pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression: 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or mUC. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or mUC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-811, when KEYTRUDA was administered in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 6% of 217 patients with locally advanced unresectable or metastatic HER2+ gastric or GEJ adenocarcinoma. The most common adverse reaction resulting in permanent discontinuation was pneumonitis (1.4%). In the KEYTRUDA arm versus placebo, there was a difference of ≥5% incidence between patients treated with KEYTRUDA versus standard of care for diarrhea (53% vs 44%) and nausea (49% vs 44%).

The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, and insomnia.

In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most common adverse reactions (≥20%) with KEYTRUDA in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%).

Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-826, when KEYTRUDA was administered in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab (n=307), to patients with persistent, recurrent, or first-line metastatic cervical cancer regardless of tumor PD-L1 expression who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent, fatal adverse reactions occurred in 4.6% of patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation, and pelvic infection. Serious adverse reactions occurred in 50% of patients receiving KEYTRUDA in combination with chemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury and sepsis (3.3% each).

KEYTRUDA was discontinued in 15% of patients due to adverse reactions. The most common adverse reaction resulting in permanent discontinuation (≥1%) was colitis (1%).

For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and decreased appetite (21%).

For patients treated with KEYTRUDA in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥20%) were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%).

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with previously treated recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with HCC were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

In KEYNOTE-581, when KEYTRUDA was administered in combination with LENVIMA to patients with advanced renal carcinoma (n=352), fatal adverse reactions occurred in 4.3% of patients. Serious adverse reactions occurred in 51% of patients, the most common (≥2%) were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction, pneumonitis, and vomiting (3% each), acute kidney injury, adrenal insufficiency, dyspnea, and pneumonia (2% each).

Permanent discontinuation of either of KEYTRUDA, LENVIMA, or both due to an adverse reaction occurred in 37% of patients; 29% KEYTRUDA only, 26% lenvatinib only, and 13% both. The most common adverse reactions (≥2%) resulting in permanent discontinuation of KEYTRUDA, LENVIMA, or the combination were pneumonitis (3%), myocardial infarction, hepatotoxicity, acute kidney injury, and rash (3% each), and diarrhea (2%).

The most common adverse reactions (≥20%) observed with KEYTRUDA in combination with LENVIMA were fatigue (63%), diarrhea (62%), musculoskeletal disorders (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), weight loss, dysphonia and proteinuria (30% each), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain and hemorrhagic events (27% each), vomiting (26%), constipation and hepatotoxicity (25% each), headache (23%), and acute kidney injury (21%).

In KEYNOTE-564, when KEYTRUDA was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in 20% of patients receiving KEYTRUDA; the serious adverse reactions (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2% including 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse reactions occurred in 21% of 488 patients; the most common (≥1%) were increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

In KEYNOTE-775, when KEYTRUDA was administered in combination with LENVIMA to patients with advanced endometrial carcinoma that were not MSI-H or dMMR (n=342), fatal adverse reactions occurred in 4.7% of patients. Serious adverse reactions occurred in 50% of these patients; the most common (≥3%) were hypertension (4.4%) and urinary tract infections (3.2%).

Discontinuation of KEYTRUDA, due to an adverse reaction occurred in 15% of these patients. The most common adverse reaction leading to discontinuation of KEYTRUDA (≥1%) was increased ALT (1.2%).

The most common adverse reactions for KEYTRUDA in combination with LENVIMA (reported in ≥20% patients) were hypothyroidism and hypertension (67% each), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53%), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), abdominal pain and weight loss (34% each), urinary tract infections (31%), proteinuria (29%), constipation (27%), headache (26%), hemorrhagic events (25%), palmar-plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%).

Adverse reactions occurring in patients with MSI-H or dMMR endometrial carcinoma who received KEYTRUDA as a single agent were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel followed by doxorubicin or epirubicin and cyclophosphamide) followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent (n=778) to patients with newly diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse reactions occurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and sepsis in association with multiple organ dysfunction syndrome and myocardial infarction. Serious adverse reactions occurred in 44% of patients receiving KEYTRUDA; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). KEYTRUDA was discontinued in 20% of patients due to adverse reactions. The most common reactions (≥1%) resulting in permanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and rash (1%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA were fatigue (70%), nausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%), decreased appetite (23%), insomnia (21%), and myalgia (20%).

In KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting (n=596), fatal adverse reactions occurred in 2.5% of patients, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA in combination with chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of patients due to adverse reactions. The most common reactions resulting in permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Pediatric Use

In KEYNOTE-051, 161 pediatric patients (62 pediatric patients aged 6 months to younger than 12 years and 99 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 24 months).

Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), vomiting (30%), leukopenia (30%), upper respiratory tract infection (29%), neutropenia (26%), headache (25%), and Grade 3 anemia (17%).

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .

About WELIREG™ (belzutifan) 40 mg tablets, for oral use

Indication in the U.S.

WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Selected Safety Information for WELIREG

Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective nonhormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

WELIREG can cause severe anemia that can require blood transfusion. In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, anemia occurred in 76% of patients and 28% had Grade 3 anemia.

Monitor for anemia before initiation of and periodically throughout treatment. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.

Transfuse patients as clinically indicated. For patients with hemoglobin (Hb) <9g/dL, withhold WELIREG until Hb≥9g/dL, then resume at reduced dose or permanently discontinue depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until Hb ≥9g/dL, then resume at a reduced dose or permanently discontinue.

The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with WELIREG.

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. In Study 004, hypoxia occurred in 1.6% of patients. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, hypoxia occurred in 29% of patients; 16% were Grade 3 hypoxia.

Monitor oxygen saturation before initiation of and periodically throughout treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

Embryo-Fetal Toxicity

Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

In Study 004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

The most common adverse reactions (≥25%) were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, the following additional adverse reactions have been reported: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration.

Drug Interactions

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

Please see Prescribing Information, including information for the Boxed Warning about embryo-fetal toxicity, for WELIREG (belzutifan) at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf and Medication Guide for WELIREG at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_mg.pdf .

About LYNPARZA ® (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

ADVERSE REACTIONS—First-Line Maintenance BRCA m Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting (SOLO-2/Study 19 ) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced g BRCA m Ovarian Cancer After 3 or More Lines of Chemotherapy

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received

LYNPARZA for advanced g BRCA m ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for advanced g BRCA m ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—Adjuvant Treatment of g BRCA m, HER2-Negative, High-Risk Early Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).

ADVERSE REACTIONS—g BRCA m, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in > 25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

ADVERSE REACTIONS—First-Line Maintenance g BRCA m Metastatic Pancreatic Adenocarcinoma

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS for LYNPARZA in the United States

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:

First-Line Maintenance BRCA m Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA -mutated (g BRCA m or s BRCA m) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

• a deleterious or suspected deleterious BRCA mutation and/or
• genomic instability

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced g BRCA m Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA- mutated (g BRCA m) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Adjuvant Treatment of g BRCA m, HER2-Negative, High-Risk Early Breast Cancer

For the adjuvant treatment of adult patients with deleterious or suspected deleterious g BRCA m, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

g BRCA m HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious g BRCA m , human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance g BRCA m Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious g BRCA m metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information , including Medication Guide .

About LENVIMA ® (lenvatinib); available as 10 mg and 4 mg capsules

LENVIMA, discovered and developed by Eisai, is a multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. The combination of LENVIMA and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone.

LENVIMA ® (lenvatinib) Indications in the U.S.

• For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)
• In combination with KEYTRUDA, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC)
• In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
• For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
• In combination with KEYTRUDA, for the treatment of patients with advanced endometrial carcinoma (EC) that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Selected Safety Information for LENVIMA

Warnings and Precautions

Hypertension. In DTC (differentiated thyroid cancer), hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC (renal cell carcinoma), hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In HCC (hepatocellular carcinoma), hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials.

Among patients receiving LENVIMA with pembrolizumab, arterial thrombotic events of any severity occurred in 5% of patients in CLEAR, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).

Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established, and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients; 2% of patients discontinued LENVIMA due to hepatic encephalopathy, and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus–treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Across clinical studies of 1823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Impaired Wound Healing. Impaired wound healing has been reported in patients who received LENVIMA. Withhold LENVIMA for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LENVIMA after resolution of wound healing complications has not been established.

Osteonecrosis of the Jaw (ONJ). ONJ has been reported in patients receiving LENVIMA. Concomitant exposure to other risk factors, such as bisphosphonates, denosumab, dental disease, or invasive dental procedures, may increase the risk of ONJ.

Perform an oral examination prior to treatment with LENVIMA and periodically during LENVIMA treatment. Advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with LENVIMA and throughout treatment with LENVIMA.

Avoid invasive dental procedures, if possible, while on LENVIMA treatment, particularly in patients at higher risk. Withhold LENVIMA for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of ONJ.

Withhold LENVIMA if ONJ develops and restart based on clinical judgement of adequate resolution.

Embryo‐Fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose.

In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥20%) observed in LENVIMA + pembrolizumab-treated patients were fatigue (63%), diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), decreased weight (30%), dysphonia (30%), proteinuria (30%), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain (27%), hemorrhagic events (27%), vomiting (26%), constipation (25%), hepatotoxicity (25%), headache (23%), and acute kidney injury (21%).

Fatal adverse reactions occurred in 4.3% of patients receiving LENVIMA in combination with pembrolizumab, including cardio-respiratory arrest (0.9%), sepsis (0.9%), and one case (0.3%) each of arrhythmia, autoimmune hepatitis, dyspnea, hypertensive crisis, increased blood creatinine, multiple organ dysfunction syndrome, myasthenic syndrome, myocarditis, nephritis, pneumonitis, ruptured aneurysm and subarachnoid hemorrhage.

Serious adverse reactions occurred in 51% of patients receiving LENVIMA and pembrolizumab. Serious adverse reactions in ≥2% of patients were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%), and pneumonia (2%).

Permanent discontinuation of LENVIMA, pembrolizumab, or both due to an adverse reaction occurred in 37% of patients; 26% LENVIMA only, 29% pembrolizumab only, and 13% both drugs. The most common adverse reactions (≥2%) leading to permanent discontinuation of LENVIMA, pembrolizumab, or both were pneumonitis (3%), myocardial infarction (3%), hepatotoxicity (3%), acute kidney injury (3%), rash (3%), and diarrhea (2%).

Dose interruptions of LENVIMA, pembrolizumab, or both due to an adverse reaction occurred in 78% of patients receiving LENVIMA in combination with pembrolizumab. LENVIMA was interrupted in 73% of patients and both drugs were interrupted in 39% of patients. LENVIMA was dose reduced in 69% of patients. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were diarrhea (26%), fatigue (18%), hypertension (17%), proteinuria (13%), decreased appetite (12%), palmar-plantar erythrodysesthesia (11%), nausea (9%), stomatitis (9%), musculoskeletal pain (8%), rash (8%), increased lipase (7%), abdominal pain (6%), and vomiting (6%), increased ALT (5%), and increased amylase (5%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

In EC, the most common adverse reactions (≥20%) observed in LENVIMA + pembrolizumab-treated patients were hypothyroidism (67%), hypertension (67%), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53%), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), decreased weight (34%), abdominal pain (34%), urinary tract infection (31%), proteinuria (29%), constipation (27%), headache (26%), hemorrhagic events (25%), palmar‐plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%).

Fatal adverse reactions occurred in 4.7% of those treated with LENVIMA and pembrolizumab, including 2 cases of pneumonia, and 1 case of the following: acute kidney injury, acute myocardial infarction, colitis, decreased appetite, intestinal perforation, lower gastrointestinal hemorrhage, malignant gastrointestinal obstruction, multiple organ dysfunction syndrome, myelodysplastic syndrome, pulmonary embolism, and right ventricular dysfunction.

Serious adverse reactions occurred in 50% of patients receiving LENVIMA and pembrolizumab. Serious adverse reactions with frequency ≥3% were hypertension (4.4%), and urinary tract infection (3.2%).

Discontinuation of LENVIMA due to an adverse reaction occurred in 26% of patients. The most common (≥1%) adverse reactions leading to discontinuation of LENVIMA were hypertension (2%), asthenia (1.8%), diarrhea (1.2%), decreased appetite (1.2%), proteinuria (1.2%), and vomiting (1.2%).

Dose reductions of LENVIMA due to adverse reactions occurred in 67% of patients. The most common (≥5%) adverse reactions resulting in dose reduction of LENVIMA were hypertension (18%), diarrhea (11%), palmar-plantar erythrodysesthesia syndrome (9%), proteinuria (7%), fatigue (7%), decreased appetite (6%), asthenia (5%), and weight decreased (5%).

Dose interruptions of LENVIMA due to an adverse reaction occurred in 58% of these patients. The most common (≥2%) adverse reactions leading to interruption of LENVIMA were hypertension (11%), diarrhea (11%), proteinuria (6%), decreased appetite (5%), vomiting (5%), increased alanine aminotransferase (3.5%), fatigue (3.5%), nausea (3.5%), abdominal pain (2.9%), weight decreased (2.6%), urinary tract infection (2.6%), increased aspartate aminotransferase (2.3%), asthenia (2.3%), and palmar-plantar erythrodysesthesia (2%).

Use in Specific Populations

Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after the last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or EC and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end-stage renal disease.

No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment is recommended for patients with DTC, RCC, or EC and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or EC and severe hepatic impairment.

Please see Prescribing Information for LENVIMA (lenvatinib) at

http://www.lenvima.com/pdfs/prescribing-information.pdf .

About the AstraZeneca and Merck strategic oncology collaboration

In July 2017, AstraZeneca and Merck, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop this product in combination with other potential new medicines and as monotherapies. Independently, the companies will develop this oncology product in combination with their respective PD-L1 and PD-1 medicines.

About the Merck and Eisai strategic collaboration

In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy KEYTRUDA.

In addition to ongoing clinical studies evaluating the KEYTRUDA plus LENVIMA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumor types across more than 20 clinical trials.

Merck’s focus on cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials .

About Merck

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• Racial and Ethnic Disparities in Cancer Clinical Trial Participation JAMA Network Open Invited Commentary July 21, 2023 Joseph M. Unger, PhD, MS

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Pittell H , Calip GS , Pierre A, et al. Racial and Ethnic Inequities in US Oncology Clinical Trial Participation From 2017 to 2022. JAMA Netw Open. 2023;6(7):e2322515. doi:10.1001/jamanetworkopen.2023.22515

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Racial and Ethnic Inequities in US Oncology Clinical Trial Participation From 2017 to 2022

• 1 Flatiron Health Inc, New York, New York
• 2 Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois Chicago, Chicago
• 3 Memorial Sloan Kettering Cancer Center, New York, New York
• 4 Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
• 5 Program on Medicines and Public Health, School of Pharmacy, University of Southern California, Los Angeles
• Invited Commentary Racial and Ethnic Disparities in Cancer Clinical Trial Participation Joseph M. Unger, PhD, MS JAMA Network Open

Question   How did racial and ethnic inequities in oncology clinical trial participation persist between 2017 and 2022?

Findings   In this cohort study of 50 411 participants and 5 cancer types, Latinx and non-Latinx Black patients had lower participation in oncology trials than non-Latinx White patients. Furthermore, during the COVID-19 pandemic (2020-2022), there were greater inequities in participation between Black and White patients compared with before the pandemic (2017-2019).

Meaning   These findings reinforce the need for guidance from regulatory agencies to improve enrollment of participants from historically excluded racial and ethnic populations in oncology trials.

Importance   There is increasing recognition from regulatory agencies that racial and ethnic representation in clinical trials is inadequate and linked to health inequities. The extent of racial inequities in clinical trial participation is unclear because prior studies have synthesized enrollment data from published trials, which often do not report participant race and ethnicity.

Objective   To evaluate racial and ethnic inequities in oncology clinical trial participation in a contemporary cohort of patients with cancer before and during the COVID-19 pandemic.

Design, Setting, and Participants   This cohort study used a nationwide electronic health record–derived deidentified database, which includes data for approximately 280 US cancer clinics (approximately 800 sites of care). The study included Latinx, non-Latinx Black (hereinafter, Black), and non-Latinx White (reference; hereinafter, White) patients aged 18 years or older who had been diagnosed with advanced non–small cell lung cancer, metastatic colorectal cancer, metastatic breast cancer, multiple myeloma, or metastatic pancreatic cancer between January 1, 2017, and June 30, 2022 (follow-up through December 31, 2022). Data analysis was performed between August 1, 2022, and February 7, 2023.

Exposures   Electronic health record–documented race and ethnicity.

Main Outcomes and Measures   The main outcome was oncology trial participation (ie, receipt of a clinical study drug). Stratified cause-specific hazard models were used to estimate adjusted hazard ratios (HRs) and 95% CIs for likelihood of participation. Participation was assessed overall, by cancer type, and by period of diagnosis (2017-2019 vs 2020-2022).

Results   Of the 50 411 patients in this study, 28 878 (57.3%) were women and 21 533 (42.7%) were men. Black and Latinx patients were younger than White patients, with a median age of 65 (IQR, 57-72), 64 (IQR, 54-73), and 68 (IQR, 60-76) years, respectively. Oncology trial participation was lower among Black patients (307 of 6912 [4.4%]) and Latinx patients (166 of 3973 [4.2%]) relative to White patients (2858 of 39 526 [7.2%]) over the entire study period. Inequities in participation were observed across the 5 cancer types studied, with notably large inequities observed among Black patients (HR, 0.54 [95% CI, 0.36-0.81]) and Latinx patients (HR, 0.46 [95% CI, 0.27-0.77]) with metastatic pancreatic cancer. Moreover, inequities between Black and White patients in terms of participation widened among those diagnosed in the COVID-19 era (2020-2022: HR, 0.49 [95% CI, 0.40-0.60] vs 1.00 [95% CI, 0.93-1.09]) relative to those diagnosed before the pandemic (2017-2019: HR, 0.61 [95% CI, 0.53-0.70] vs 1 [reference]).

Conclusions and Relevance   The findings of this cohort study suggest that oncology trial participation was lower among Black and Latinx patients relative to White patients across all 5 cancer types examined. These findings, including potentially widening inequities in the COVID-19 era, support the need for regulatory guidance to improve enrollment of participants from historically excluded racial and ethnic populations in clinical trials.

US Food and Drug Administration (FDA) draft guidance from April 2022 calls for the improvement of clinical trial enrollment of participants from historically excluded racial and ethnic populations, and key organizations have made similar calls for more diverse representation among oncology trial participants. 1 , 2 Earlier research offered evidence of racial and ethnic inequities in clinical trial participation, but such studies analyzed enrollment data from published trials, which often lack information on participant race and ethnicity. 3 Given evidence of worsening racial and ethnic inequities in access to health care and health outcomes, especially since the start of the COVID-19 pandemic, this study aimed to assess the extent of racial and ethnic inequities in oncology clinical trial participation and how they may have changed in recent years. 4

This retrospective cohort study used the nationwide electronic health record (EHR)–derived deidentified database from Flatiron Health Inc. This database is longitudinal and comprises deidentified patient-level structured and unstructured data curated via technology-enabled abstraction. 5 , 6 During the study period, the deidentified data originated from approximately 280 US cancer clinics (approximately 800 sites of care). This study included 50 411 patients, with diagnoses of advanced non–small cell lung cancer (n = 20 961), metastatic colorectal cancer (n = 10 596), metastatic breast cancer (n = 9912), multiple myeloma (n = 4348), or metastatic pancreatic cancer (n = 4594). These are among the most common cancers in the US and cancers with known inequities in incidence and survival. 7 The cohort was limited to patients aged 18 years or older with a confirmed diagnosis between January 1, 2017, and June 30, 2022 (follow-up through December 31, 2022). We excluded patients with potentially incomplete therapy data (ie, discrepancies between unstructured and structured treatment records) and patients without a documented race and ethnicity (25.3% of otherwise eligible patients). The attrition table is presented in the eTable in Supplement 1 .

Institutional review board approval of the study was obtained by Flatiron Health and included a waiver of informed consent because deidentified data were used. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

We examined oncology trial participation by EHR-documented race and ethnicity and focused on Latinx, non-Latinx Black (hereinafter, Black), and non-Latinx White (hereinafter, White) patients. We excluded non-Latinx Asian patients from the analysis because the relatively small sample size may offer imprecise estimates of participation rates. We also excluded patients with a documented race of “other” due to the unclear interpretation of such results (ie, multiple racial groups are masked as “other” for privacy reasons; additional details are provided in the eTable in Supplement 1 ). Race and ethnicity values vary by practices at individual clinical sites and the limitations of the EHR software used. Although they are likely to reflect self-reported assignments by patients, it is unknown whether these values are self-reported or clinician or staff reported. Trial participation was defined as EHR-documented receipt of a clinical study drug during an oncologist-defined, rule-based line of therapy. We reported participation rates and used Cox proportional hazard models to estimate hazard ratios (HRs) of participation, which accounted for differences in follow-up time after adjusting for clinical factors such as age, gender (detailed in Table 1 ), Eastern Cooperative Oncology Group performance status, year of diagnosis, and cancer type. In an exploratory analysis, we estimated models stratified by cancer and year of diagnosis, with the latter comparing trial participation between patients diagnosed in the pre–COVID-19 and COVID-19 eras (2017-2019 vs 2020-2022). We conducted all statistical analyses using R, version 4.0.2, from August 1, 2022, to February 7, 2023. Estimates are presented with 95% CIs.

Of the 50 411 patients in this study, 28 878 (57.3%) were women and 21 533 (42.7%) were men. Table 1 summarizes the cohort characteristics. With regard to race and ethnicity, 6912 patients (13.7%) were Black, 3973 (7.9%) were Latinx, and 39 526 (78.4%) were White. Black and Latinx patients were younger than White patients, with a median age of 65 (IQR, 57-72), 64 (IQR, 54-73), and 68 (IQR, 60-76) years, respectively. Metastatic colorectal cancer was the most common type among Latinx patients, whereas advanced non–small cell lung cancer was the most common type among Black and White patients. Notably, 938 of 4348 patients (21.6%) with multiple myeloma were Black, denoting a greater prevalence of this cancer among Black patients in the cohort.

Table 2 lists oncology trial participation by race and ethnicity. Overall participation was 4.4% (307 of 6912) among Black patients, 4.2% (166 of 3973) among Latinx patients, and 7.2% (2858 of 39 526) among White patients. Absolute differences in participation were greatest among patients with metastatic pancreatic cancer (25 of 487 Black patients [5.1%] and 16 of 332 Latinx patients [4.8%] vs 370 of 3775 White patients [9.8%]). The lowest absolute rates of participation were observed among Latinx patients, with rates of 3.5% (43 of 1222) for metastatic colorectal cancer trials and 3.2% (34 of 1047) for metastatic breast cancer trials; this contrasted with metastatic colorectal cancer as the most common cancer among Latinx patients in the cohort. In adjusted models, Black and Latinx patients were less likely to participate in clinical trials than White patients in all disease states with all 95% CIs below 1 (with the exception of Latinx patients with multiple myeloma).

Table 3 lists oncology trial participation in our exploratory analysis by year of diagnosis, comparing participation between patients diagnosed in the pre–COVID-19 and COVID-19 eras. Overall participation was lower among Black and Latinx patients in both periods relative to White patients. Specifically, the likelihood of trial participation among Black patients in the COVID-19 era was lower relative to the pre–COVID-19 era (2017-2019: HR, 0.61 [95% CI, 0.53-0.70] vs 2020-2022: HR, 0.49 [95% CI, 0.40-0.60]), whereas the likelihood of participation among White patients did not meaningfully change over time (2017-2019: HR, 1 [reference] vs 2020-2022: HR, 1.00 [95% CI, 0.93-1.09]).

These findings suggest that racial and ethnic inequities in oncology clinical trial participation persisted from 2017 to 2022 and may have widened since the start of the COVID-19 pandemic. We observed lower participation among Black and Latinx patients (relative to White patients) across the cancers studied, which underscores the importance of the recent FDA draft guidance for diversity plans to improve enrollment of participants from underrepresented racial and ethnic populations in clinical trials. 1 , 2 Many published clinical trials have not reported participant race and ethnicity. 3 Therefore, EHR-derived data can be used to elucidate persistent inequities in cancer trial participation.

The historical underrepresentation of Black and Latinx patients in oncology clinical trials is in stark contrast with the higher cancer incidence and known inequities in cancer outcomes, particularly in pancreatic cancer and multiple myeloma, which can exacerbate cancer inequities through the exclusion of such groups from investigational drug access. 8 , 9 Broadly, the COVID-19 pandemic has deepened the extent of health inequities between racial and ethnic groups, and our study offers evidence that inequities between Black and White patients with cancer may have worsened following the pandemic. 4 Additional work is needed to confirm whether these trends have persisted since the start of the pandemic. Beyond the FDA draft guidance intended for industry sponsors of clinical trials, there is further opportunity to potentially address these and other trial inequities through advances in technology. Digital tools that automate patient screening and trial matching have the ability to more easily evaluate larger patient populations for eligibility in an unbiased manner, potentially reducing the burden on research teams while also expanding enrollment opportunities. 10 Similarly, equitable decentralization of clinical trials may help to reduce financial or transportation barriers to clinical trial participation, as could broadening eligibility criteria to improve trial access for all—although these hypotheses are yet to be proven. 11 , 12 The outcomes of such strategies on narrowing clinical trial inequities should be a focus of future research. 13 By bridging the divide between routine care and clinical research, integrated evidence has the opportunity to make clinical trial participation more available to patients, increasing the potential depth of data, representativeness, and efficiency of clinical research. 14

Our findings on greater inequities in cancer clinical trial participation among Black patients during the COVID-19 pandemic add to the growing evidence on pandemic-related decreases in participation in clinical trials. In an interrupted time-series analysis of trials conducted between 2016 and 2021 in the SWOG Cancer Research Network, 15 the total number of patients enrolled in clinical trials decreased during the first year of the pandemic. However, enrollment reductions were primarily to cancer control and prevention trials, whereas evidence of enrollment reductions to treatment trials was lacking. Distinct from the SWOG analysis, an exploratory objective of our study was to examine clinical trial participation in the COVID-19 era; although there was little evidence of statistical interaction (post hoc analysis) between year of diagnosis and racial and ethnic group, we estimated race- and time period–specific estimates of clinical trial participation. Also, we defined participation differently than the analysis of SWOG trials, which may have implications for how we interpret and compare results from the postpandemic time period, such as the different settings for industry-sponsored trials and our inclusion of Latinx patients in our analysis. These differences highlight the importance of carefully considering the context and methodology of each study when interpreting and comparing rates of cancer clinical trial participation.

Historically marginalized or minoritized groups, including Black and Latinx patients, women, and patients aged 65 years or older, are consistently underrepresented in clinical trials, considering their disproportionate burden of cancer incidence. 16 - 18 In a study of landmark trials that led to FDA oncology drug approvals, Loree et al 19 found that compared with rates of US cancer incidence, Black and Latinx patients with cancer were underrepresented in oncology trials (22% and 44% of expected, respectively) compared with White patients with cancer (98% of expected). This lack of representation of patients with cancer from historically marginalized groups may be explained, in part, by the contributions (or lack thereof) of industry-sponsored trials relative to federally sponsored trials. In an analysis of 358 oncology clinical trials of 93 825 patients across 15 cancer types between 2008 and 2018, the overall proportion of Black patients represented was 2.9% for industry-sponsored trials and 9.0% for National Cancer Institute–sponsored trials. 20

The barriers to recruitment and participation of historically marginalized, minoritized, and excluded patients in cancer clinical trials are considerable. In a systematic review of 65 oncology therapeutic and cancer prevention trials, multiple barriers to the awareness (eg, education on clinical trials), opportunity (eg, eligibility, lack of communication), and ultimately participation (eg, mistrust, costs, transportation) were consistently reported. 21 The effects of language barriers and lack of culturally relevant education about clinical trials were also frequently reported. Although there are often multiple proposed ways to improve opportunities for enrollment and participation, including using less rigid study designs and developing systems that facilitate the participation of health care professionals, the steps taken by investigators and drug sponsors to increase enrollment too often will prove inadequate in the absence of an organizational and technology infrastructure to support contemporary trials. 22 , 23 Opportunities exist for digital tools and empirical data from clinical practice to potentially reduce the diversity gap between the underlying patient population and those that are eligible and subsequently enrolled in clinical trials. In a study using administrative claims data, Riner et al 24 determined how inclusion and exclusion criteria can result in disparities in pancreatic ductal adenocarcinoma clinical trial eligibility. These empirical data demonstrated that revising certain eligibility criteria (eg, comorbidities and measures of kidney function) resulted in similar rates of eligibility between racial groups.

This study has some limitations. First, our use of clinical study drug administration as a surrogate for oncology trial participation likely underrepresents clinical trial accrual, since it may not capture participation in surgery, radiation, observational, or nontreatment interventional trials and is reliant on EHR documentation. Second, we were unable to examine inequities in clinical trial participation among other historically excluded groups due to data deidentification processes and small cohort sizes; further work is needed to investigate the potential for such inequities. Third, we excluded patients without a documented race or ethnicity from our analysis; thus, our results may be an underestimation of the inequities in participation among Black and Latinx patients. Finally, the generalizability of these results to the broader US oncology population may be limited, as we focused on a select group of cancers and the composition of the Flatiron Health population can differ in certain aspects from the US oncology population (eg, distribution of race and ethnicity not similar to that observed in other national databases). 5

In this cohort study of racial and ethnic inequities in oncology clinical trial participation, we observed that Latinx and Black patients had lower participation in oncology trials than White patients across the 5 cancer types studied over the 2017 to 2022 study period. Our findings support the FDA recommendation for diversity plans that aim to improve enrollment of participants from historically excluded racial and ethnic populations in clinical trials, particularly given evidence of worsening inequities observed during the COVID-19 era.

Accepted for Publication: May 16, 2023.

Published: July 21, 2023. doi:10.1001/jamanetworkopen.2023.22515

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License . © 2023 Pittell H et al. JAMA Network Open .

Corresponding Author: Gregory S. Calip, PharmD, MPH, PhD, Flatiron Health Inc, 233 Spring St, New York, NY 10013 ( [email protected] ).

Author Contributions: Drs Pittell and Guadamuz had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Pittell and Calip contributed equally to this work.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Pittell, Calip, Ryals, Altomare, Royce, Guadamuz.

Drafting of the manuscript: Pittell, Calip, Altomare, Royce, Guadamuz.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Pittell, Calip, Guadamuz.

Administrative, technical, or material support: Pittell, Calip, Ryals, Altomare, Royce.

Supervision: Calip, Ryals, Altomare, Royce, Guadamuz.

Conflict of Interest Disclosures: Dr Pittell reported being employed by Flatiron Health, and owning stock in Roche during the conduct of the study. Dr Calip reported being employed by Flatiron Health and owning stock in Roche during the conduct of the study and receiving grants from Pfizer awarded to the University of Illinois Chicago outside the submitted work. Ms Pierre reported being employed by Flatiron Health and owning stock in Roche during the conduct of the study and receiving personal fees from the Pfizer Health Equity in Action Summit outside the submitted work. Dr Ryals reported being employed by Flatiron Health and owning stock in Roche during the conduct of the study and receiving grants from the National Cancer Institute outside the submitted work. Dr Altomare reported being employed by Flatiron Health and owning stock in Roche during the conduct of the study. Dr Royce reported being employed by Flatiron Health and owning stock in Roche during the conduct of the study and owning stock in Lumata Health, VitriVax, and Agilix Health outside the submitted work. Dr Guadamuz reported being employed by Flatiron Health and owning stock in Roche during the conduct of the study.

Funding/Support: This study was sponsored by Flatiron Health Inc, which is an independent member of the Roche Group.

Role of the Funder/Sponsor: Flatiron Health was involved in the review and approval of the manuscript but was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation of the manuscript; and decision to submit the manuscript for publication. The parent company (Roche Group) was not involved in the design or any aspect of the conduct of the study.

Meeting Presentation: Results from this study were presented, in part, at the annual conference of the International Society for Pharmacoepidemiology; August 28, 2022; Copenhagen, Denmark.

Data Sharing Statement: See Supplement 2 .

Additional Contributions: We thank the following Flatiron Health employees: Sandy Griffith, PhD, and Rebecca Miksad, MD, MPH, for constructive feedback, which has helped improve the scientific rigor of this manuscript; and Hannah Gilham, MFA, and Darren Johnson, PhD, for providing writing and editing support. No financial compensation was provided for these contributions.

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Simple 'swish-and-spit' oral rinse could provide early screening for gastric cancer

by Digestive Disease Week

A simple oral rinse could provide early detection of gastric cancer, the fourth-leading cause of cancer deaths worldwide, according to a study scheduled for presentation at Digestive Disease Week (DDW) 2024.

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Researchers analyzed bacteria samples from the mouths of 98 patients scheduled for endoscopy, including 30 known to have gastric cancer , 30 with premalignant gastric conditions and 38 healthy controls. They found distinct differences between the oral microbiomes of the healthy group compared to the cancerous and pre-cancerous patients.

They also found very little difference between the samples from pre-malignant patients and those with cancer, suggesting that the changes in the microbiome may occur as soon as the stomach environment starts to undergo changes that can eventually turn into cancer.

"We see that the oral microbiome and the stomach microbiome are connected, and knowing what bugs are in your mouth tells us what the stomach environment is like," Perati said. "That has a huge implication that could lead to some practice-changing tests and guidelines."

The findings suggest that oral bacteria alone could be biomarkers for gastric cancer risk. Based on their findings, the authors developed a model of the 13 bacterial genera representing the most significant differences between controls and the cancer and pre-cancer patients.

"No formal screening guidelines for gastric cancer are available in the United States, and more than half of patients with gastric cancer receive a diagnosis when the cancer is already at an advanced stage ," Perati said.

Researchers plan to conduct larger studies in multiple institutions to ensure findings are generalizable to a wider population.

"Even with a small cohort, we were able to see some stark differences and believe the findings are very promising," Perati said.

Dr. Perati will present data from the study, "Oral microbiome signatures as potential biomarkers for gastric cancer risk assessment," abstract 949, on Monday, May 20, at 4:15 p.m. EDT.

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