Plain Language Summary
What is this summary about?
This is a summary of the publication of the EV-302/KEYNOTE-A39 study that was published in The New England Journal of Medicine in March 2024. The study helped researchers learn more about a possible new treatment for advanced urothelial cancer. Urothelial cancer starts in the bladder or other parts of the urinary tract.Platinum-based chemotherapy is usually the first therapy used to treat advanced urothelial cancer, but platinum-based chemotherapy does not always work and can have many side effects. In this study, researchers tested how well the study drug enfortumab vedotin (EV),when given with another anticancer drug called pembrolizumab, worked compared to platinum-based chemotherapy in participants with advanced urothelial cancer.
What are the key takeaways?
Researchers found that overall, participants who received EV (enfortumab vedotin) with pembrolizumab lived about 2 times longer without their cancer growing or spreading after starting treatment compared to participants who received platinum-based chemotherapy.
Researchers also found that overall, people who received EV with pembrolizumab lived almost 2 times longer after starting treatment compared to participants who received platinum-based chemotherapy.
Almost all participants in both treatment groups had a side effect that happened during the study that was possibly related to their study treatment. About 6 in 10 participants who received EV with pembrolizumab, and about 7 in 10 participants who received platinum-based chemotherapy, had a severe side effect during the study that was possibly related to their study treatment.
For participants who received EV with pembrolizumab, the most common side effect was weakness, numbness, and pain from nerve damage in the hands and feet. For participants who received platinum-based chemotherapy, the most common side effect was low numbers of red blood cells (anemia).
What were the main conclusions reported by the researchers?
Overall, researchers found that EV with pembrolizumab helped participants live longer without their cancer growing or spreading,and helped participants live longer in general , compared to platinum-based chemotherapy. Researchers believe EV with pembrolizumab should be a standard treatment option for most people who have advanced urothelial cancer that has not been treated previously with other anticancer drugs. People who receive EV with pembrolizumab should closely monitor their health and inform their healthcare team of signs of weakness, numbness, or pain in their hands and feet, or other potential side effects such as skin rashes.
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Acknowledgments
The authors would like to thank the clinical study participants and their family members and caregivers. They would also like to thank the staff members at the study centers who cared for the participants in the clinical study.
Funding
This manuscript was funded by Seagen Inc., which was acquired by Pfizer in December 2023, and Astellas Pharma Inc. The funder collaborated with the authors on the preparation of this plain language summary.
Declaration of interests
Astellas Pharma Inc., Northbrook, IL, USA; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; and Seagen, Bothell, WA, USA, which was acquired by Pfizer in December 2023, funded this study. The study was designed by Astellas Pharma Inc. and Pfizer and led by Pfizer for data collection and analysis and was approved by the institutional review board at each partnering site. All authors and sponsors assisted in data interpretation, wrote the report, reviewed the manuscript, and provided final approval to submit the manuscript for publication. Thomas Powles reports research funding to their institution from Astellas Pharma,AstraZeneca, Bristol-Myers Squibb, Eisai, EMD Serono, Inc., Exelixis, F. Hoffmann-La Roche, Gilead Sciences Inc., Hoffmann-La Roche Limited, Ipsen Biopharm Limited,Johnson & Johnson Health Care Systems Inc., Merck, MSD, Novartis, Pfizer, and Seattle Genetics, Inc.; consultant roles with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Eisai, EMD Serono, Inc., Exelixis, F. Hoffmann-La Roche, Gilead Sciences Inc., Incyte Corporation, Ipsen Biopharm Limited, Johnson & Johnson Health Care Systems Inc., Mashup Communications, Merck, MSD, Novartis, Pfizer, and Seattle Genetics, Inc.; paid travel from AstraZeneca, F. Hoffmann-La Roche, Gilead Sciences Inc., Ipsen Biopharm Limited, Mashup Communications, Merck, MSD, and Pfizer; strategic advisory positions with Bristol-Myers Squibb, F. Hoffmann-La Roche, and Pfizer; and is a medical oncology consultant at Queen Mary University of London. Begoña P. Valderrama reports consultant roles with Advanced Accelerator Applications, Astellas Pharma, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, EUSA Pharma, Ipsen Biopharmaceuticals, Inc., Janssen Cilag EMEA,Merck, Novartis Pharma, and Pfizer; paid speaking engagements from Astellas Pharma, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, EUSA Pharma, and Merck; paid travel from Astellas Pharma Bristol-Myers Squibb, F. Hoffmann-La Roche, Ipsen Biopharmaceuticals, Inc., and Pfizer; and reports consultant role for their spouse/partner from Merck Sharp and Dohme. Shilpa Gupta reports advisory board positions with Astellas Pharma US Inc., Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Foundation Medicine, Inc., Genzyme Corporation, Gilead Sciences Inc., Guardant Health,Janssen Biotech, Inc., Merck Sharp and Dohme Corporation, Natera, Pfizer, and Seattle Genetics, Inc.; other consultant roles with AstraZeneca and EMD Serono, Inc.;owns stock with BioNTech and Nektar Therapeutics; paid travel from Bristol-Myers Squibb Company; paid speaking engagements with Bristol-Myers Squibb Company, Gilead Sciences Inc., Janssen Biotech, Inc., and Seattle Genetics, Inc.; research funding to their institution from Merck Sharp and Dohme Corporation and Seattle Genetics, Inc. Jens Bedke reports advisory board positions at Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Eisai, Ipsen, Janssen Pharmaceuticals,Merck Sorono, Merck Sharp and Dohme, Pfizer, and Roche; research funding to their institution from Astellas, AstraZeneca, Bristol-Myers Squibb, Eisai, Ipsen, Merch Sharp and Dohme, Nektar, Novartis, Pfizer, Roche, and Seagen; and steering committee positions from Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, and Seagen. Eiji Kikuchi reports consultant roles with Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Janssen Biotech, Inc., Kissei, Merck, MSD,and Pfizer; paid speaking engagements with Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceuticals Co., Ltd., Janssen Biotech, Inc., Kissei, Merck, MSD,Nippon Kayaku, Pfizer, and Taiho Pharmaceutical. Jean Hoffman-Censits reports institutional research support from Daiichi Sankyo, EMD Serono, and Ikena Oncology,Seagen; grant support from Roche/Genentech; and consulting fees from Gilead Sciences. Gopa Iyer reports consultant roles at Bicycle Therapeutics, EMD Serono,Flare Therapeutics, Janssen Research & Development, LLC, and Loxo Oncology; research funding to their institution from Loxo Oncology, Mirati Therapeutics,Seagen Inc., and Tyra Biosciences. Christof Vulsteke reports advisory board positions with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Ipsen Biopharm Limited, Janssen Pharmaceuticals, Merck Sharp and Dohme, and Pfizer; and research funding to their institution from Merck Sharp and Dohme. Se Hoon Park has no financial interests to report. Sang Joon Shin has no financial interests to report. Daniel Castellano Gauna reports scientific advisory board positions at Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Exelixis, F. Hoffman La Roche, Ipsen Pharma SAS, Janssen Pharmaceuticals, Johnson & Johnson Health Care Systems Inc., Merck Sharp and Dohme, Novartis, Pfizer, and Seagen Inc. Giuseppe Fornarini reports interests with Amgen, Astellas Pharma, Bristol-Myers Squibb, and Eisai; a consultant position at Astellas Pharma; and paid travel from Merck and Novartis. Jian-Ri Li has no financial interests to report. Mahmut Gumus reports advisory board positions at AbbVie, Astellas Pharma, Gilead Sciences, and Novartis; research grants to their institution from Amgen and F. Hoffmann-La Roche; paid speaking engagements with AstraZeneca, Bristol-Myers Squibb, and Takeda Oncology; paid travel from F. Hoffman-La Roche and Regeneron Pharmaceuticals; professorships at Istanbul Medeniyet University and Dr. Suleyman Yalcin City Hospital; and principal investigator roles with Janssen Pharmaceuticals, Merck, Pfizer, and Regeneron Pharmaceuticals. Nataliya Mar reports paid speaking engagements with Eisai, Merck, and Seattle Genetics.Yohann Loriot reports advisory board positions with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, F. Hoffman-La Roche, Gilead Sciences Inc., Janssen Biotech,Merck KGaA, Merck Sharp and Dohme, Pfizer, Sanofi Pasteur Inc., Seattle Genetics, and Tahio; paid travel from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb,Janssen Biotech, Merck Sharp and Dohme, and Seattle Genetics; paid speaking engagements from AstraZeneca, F. Hoffmann-La Roche, Merck Sharp and Dohme,and Pfizer. Aude Flechon reports paid travel from Astellas European Foundation, Astellas Pharma, Bristol-Myers Squibb, Janssen Cilag EMEA, Merck, Merck Sharp and Dohme, Novartis, and Pfizer; and board positions at Astellas Pharma Europe, Bristol-Myers Squibb, Gilead Foundation, Janssen Cilag EMEA, Merck Sharp and Dohme,Novartis, and Pfizer. Ignacio Duran reports paid speaking engagements at Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, EUSA Pharma (US) LLC, Gilead Sciences Inc., Ipsen Pharma SAS, Johnson & Johnson, Merck, Merck Sharp and Dohme, Novartis, Pfizer, and Roche; scientific advisory board positions at Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, EUSA Pharma (US) LLC, Gilead Sciences Inc., Ipsen Pharma SAS, Johnson & Johnson, Merck, Merck Sharp and Dohme, Novartis, Pfizer, Pharmacyclics LLC, an AbbVie Company, Roche, and Seagen Inc.; principal investigator roles with Astellas Pharma, AstraZeneca, Bayer,Bicycle Therapeutics, Bristol-Myers Squibb, Eli Lilly, Gilead Sciences Inc., Ipsen Pharma SAS, Johnson & Johnson, Merck, Merck Sharp and Dohme, Pharmacyclics LLC,an AbbVie Company, Roche, and Seagen Inc.; research grants to their institution from AstraZeneca, Gilead Sciences, and Roche; paid travel from Bayer, Gilead Sciences Inc., Ipsen Pharma SAS, Johnson & Johnson, Merck, and Merck Sharp and Dohme; and a steering committee position at Gilead Sciences, Inc. Alexandra Drakaki reports advisory board positions at Astellas Pharma, AstraZeneca, Bristol Myers Squibb Company, Eli Lilly, EMD Serono, Exelixis Inc., F. Hoffmann La Roche,Infinity, Janssen Biotech, Inc., Merck Sharp & Dohme Corporation, PACT Pharma, Seagen Inc.; data and safety monitoring board position at Nektar; and paid consulting at Seagen Inc. Sujata Narayanan is employed at Pfizer Inc. Xuesong Yu is employed at Pfizer Inc. Seema Gorla is employed at Astellas Pharma Global Development. Blanca Homet Moreno is employed at Merck Sharp and Dohme and owns stock at Merck Sharp and Dohme. Michiel S. Van der Heijden reports advisory board positions paid to their institute with Astellas Pharma,AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, Janssen Pharmaceuticals, MerckSharp and Dohme Corporation, Pfizer, and Seagen Inc.; research funding to their institution from AstraZeneca, Bristol-Myers Squibb Company, F. Hoffmann-La Roche, and Merck Sharp and Dohme Corporation; steering committee positions paid to their institute with AstraZeneca, Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Merck Sharp and Dohme Corporation, and Seagen Inc. The authors have no other competing interests, financial involvement, or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.
Writing disclosure
Medical writing and editorial assistance in the development of this summary was funded by Seagen Inc., which was acquired by Pfizer in December 2023 and Astellas Pharma Inc. and provided by Samuel Entwisle, PhD, and Scott Finger of the Center for Information & Study on Clinical Research Participation (CISCRP), a non-profit organization focused on educating and informing the public about clinical research participation.