Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer
Is this the end of the cisplatin era in bladder cancer? It sure seems that way. The results here are no surprise based on the signal we saw in the metastatic setting.
Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer
Author(s): Christof Vulsteke, M.D., Ph.D.1,2; Nabil Adra, M.D.3; Pongwut Danchaivijitr, M.D.4; Maksym Sabadash, M.D., Ph.D.5; Alejo Rodriguez-Vida, M.D., Ph.D.6; Zhentao Zhang, M.D., Ph.D.7; Vagif Atduev, M.D.8; Y. Emre Göger, M.D.9; Steffen Rausch, M.D.10; Seok-Ho Kang, M.D., Ph.D.11; Yohann Loriot, M.D., Ph.D.12; Jens Bedke, M.D.13; Matthew D. Galsky, M.D.14; Peter H. O’Donnell, M.D.15; Gunhild von Amsberg, M.D.16; Nimira Alimohamed, M.D.17; Grzegorz Sulimka, M.D.18; Shilpa Gupta, M.D.19; Viktor Paramonov, M.D.20; Keita Nakane, M.D., Ph.D.21; Michael Mihm, Ph.D.22; Changting Meng, M.D.23; Caizhi David Huang, Ph.D.24; Chethan Ramamurthy, M.D.24; Blanca Homet Moreno, M.D., Ph.D.24; Anders Ullén, M.D., Ph.D.25,26; the KEYNOTE-905/EV-303 Investigators*;
Source: DOI: 10.1056/NEJMoa2511674
Dr. Maen Hussein's Thoughts
At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin–pembrolizumab group and 39.4% in the control group (hazard ratio) HR 0.4 estimated overall survival was 79.7% and 63.1% HR 0.50. Perioperative enfortumab vedotin plus pembrolizumab new standard of care for cisplatin ineligible patients who are candidates for surgery.
BACKGROUND
Patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy proceed directly to radical cystectomy with pelvic lymph-node dissection. Perioperative therapy may improve outcomes in this population.
METHODS
In this phase 3, open-label trial, participants with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy were randomly assigned to perioperative (neoadjuvant and adjuvant) enfortumab vedotin, an antibody–drug conjugate directed nectin-4, plus pembrolizumab and surgery (9 total cycles of enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] plus 17 total cycles of pembrolizumab [200 mg on day 1 every 3 weeks], with surgery after 3 cycles) or surgery alone (control). The primary end point was event-free survival. Key secondary end points were overall survival and pathological complete response (absence of viable tumor after surgical resection). Other secondary end points included safety. Research Summary Perioperative Enfortumab Vedotin–Pembrolizumab in Bladder Cancer
RESULTS
A total of 344 participants underwent randomization (170 in the enfortumab vedotin–pembrolizumab group and 174 in the control group). data cutoff, median follow-up was 25.6 months (range, 11.8 to 53.7). Surgery was performed in 87.6% of participants in the enfortumab vedotin–pembrolizumab group and in 89.7% in the control group. 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin–pembrolizumab group and 39.4% in the control group (hazard ratio for an event or death, 0.40; 95% confidence interval [CI], 0.28 to 0.57; two-sided P
CONCLUSIONS
Perioperative enfortumab vedotin plus pembrolizumab and surgery led to significantly better event-free and overall survival outcomes and a greater percentage of participants with pathological complete response than surgery alone in a predominantly cisplatin-ineligible population with muscle-invasive bladder cancer. Safety was also assessed. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-905 ClinicalTrials.gov number, NCT03924895.)
Author Affiliations
1Integrated Cancer Center Ghent, AZ Maria Middelares, Ghent, Belgium; 2Center for Oncologic Research, Antwerp University, Antwerp, Belgium; 3Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis; 4Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 5Lviv State Regional Oncological Center, Lviv, Ukraine; 6Hospital del Mar, Barcelona; 7Parkview Cancer Institute, Fort Wayne, IN; 8Volga District Medical Center, Federal Medical-Biologic Agency, Nizhny Novgorod, Russia; 9Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey; 10University Hospital Tübingen, Tübingen, Germany; 11Korea University Anam Hospital, Seoul, South Korea; 12Université Paris-Saclay, Gustave Roussy, INSERM Prédicteurs Moléculaires et Nouvelles Cibles en Oncologie, Villejuif, France; 13Eva Mayr-Stihl Cancer Center, Klinikum Stuttgart, Stuttgart, Germany; 14Icahn School of Medicine Mount Sinai, Tisch Cancer Institute, New York; 15University of Chicago, Chicago; 16University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 17Arthur J.E. Child Comprehensive Cancer Centre, Calgary, AB, Canada; 18Szpital Wojewódzki im. Św. Łukasza, Tarnow, Poland; 19Taussig Cancer Institute, Cleveland Clinic, Cleveland; 20Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Oblast Council, Cherkasy, Ukraine; 21Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan; 22Astellas Pharma, Northbrook, IL; 23Pfizer, Bothell, WA; 24Merck, Rahway, NJ; 25Department of Oncology–Pathology, Karolinska Institutet, Stockholm; 26Department of Pelvic Cancer, Genitourinary Oncology and Urology Unit, Karolinska University Hospital, StockholmRelated Articles
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