Pfizer, Merck Partner on Bladder Cancer Treatment with Positive Trial Results

Pfizer announced positive results for its antibody-drug conjugate Padcev combined with Merck's immunotherapy Keytruda in treating bladder cancer. The Phase 3 trial showed a "clinically relevant and statistically significant improvement" in event-free survival and improvements in overall survival and complete pathological response compared to surgery alone. This combination could be a new treatment option for bladder cancer patients, particularly those ineligible for chemotherapy.

Pfizer and Merck have announced positive results from a Phase 3 trial evaluating the combination of Padcev (enfortumab vedotin-ejfv) and Keytruda (pembrolizumab) in treating muscle-invasive bladder cancer (MIBC). The trial, known as KEYNOTE-905, demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS), the study’s primary endpoint, as well as overall survival (OS) and pathologic complete response (pCR) rate, key secondary endpoints, compared to surgery alone [1].

The study enrolled 595 patients who were randomized to receive either three cycles of preoperative Keytruda, followed by surgery to remove the bladder (radical cystectomy), followed by 14 cycles of postoperative Keytruda; surgery alone; or three cycles of preoperative Keytruda plus Padcev, followed by surgery to remove the bladder, followed by six cycles of Keytruda plus Padcev and then eight cycles of Keytruda alone. The primary objective of the trial was to compare EFS between the combination therapy arm and surgery alone, with secondary objectives including OS and pCR rate [1].

The results indicate that the combination therapy significantly improved EFS, OS, and pCR rate compared to surgery alone, marking the first time a systemic treatment approach has shown a survival advantage over standard-of-care surgery in this cisplatin-ineligible patient population. This represents a significant advancement in the treatment of MIBC, particularly for patients who are ineligible for cisplatin-based chemotherapy [1].

The study was conducted in collaboration with Pfizer and Astellas, and builds on the clinical success of the combination in locally advanced or metastatic urothelial cancer. Merck and Pfizer plan to share these results with regulatory authorities worldwide and will present the data at an upcoming medical meeting [1].

The safety profile of the combination therapy was consistent with the known safety profiles of each agent, with no new safety signals identified. Keytruda plus Padcev is already approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer in several countries, including the U.S., the European Union, Japan, and several other countries around the world [1].

This development could provide a new treatment option for bladder cancer patients, particularly those who are ineligible for chemotherapy, addressing a critical unmet need in this vulnerable population. Merck is currently evaluating Keytruda across all stages of bladder cancer, including non-muscle-invasive, muscle-invasive, and metastatic, with several Phase 3 studies ongoing [1].

References:
[1] https://www.merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-significantly-improved-event-free-and-overall-survival-and-pathologic-complete-response-rate-for-certain-patients-with-muscle/