Keytruda Plus Padcev Combination Significantly Improves Survival in Muscle-Invasive Bladder Cancer

Merck (known as MSD outside the U.S. and Canada) has announced transformative topline results from the Phase 3 KEYNOTE-B15 trial (also referred to as EV-304). The study demonstrates that the combination of KEYTRUDA (pembrolizumab) and Padcev (enfortumab vedotin-ejfv) significantly improves outcomes for patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy.

This breakthrough, developed in collaboration with Pfizer and Astellas, marks a potential shift in the standard of care for patients at an earlier stage of the disease, where the risk of recurrence remains high despite surgery.

Trial Results: Redefining Success in MIBC

The trial compared the KEYTRUDA plus Padcev regimen (given both before and after surgery) against the current standard of care—neoadjuvant chemotherapy followed by surgery. The combination met its primary and key secondary endpoints:

Event-Free Survival (EFS): A statistically significant improvement in the time patients lived without disease progression or recurrence.
Overall Survival (OS): A meaningful increase in the total lifespan of patients compared to those receiving traditional chemotherapy.
Pathologic Complete Response (pCR): A higher rate of patients showing no signs of cancer in their tissue samples after the initial phase of treatment.

The Treatment Regimen

The KEYNOTE-B15 trial enrolled 808 patients, randomized into two specific arms:

Combination Arm: Four 21-day cycles of neoadjuvant (pre-surgery) KEYTRUDA plus Padcev, followed by surgery (radical cystectomy), and then 13 cycles of adjuvant (post-surgery) KEYTRUDA with five additional cycles of Padcev.
Standard Arm: Four 21-day cycles of standard neoadjuvant chemotherapy (gemcitabine plus cisplatin) followed by surgery.

Expert Insights

The medical community views these results as a major step forward in treating “high-risk” bladder cancer patients before the disease spreads to other organs.

“The strength of these data demonstrates that pembrolizumab plus enfortumab vedotin—given before and after surgery—has the potential to significantly improve survival outcomes.” — Dr. Matthew Galsky, Principal Study Investigator, Mount Sinai Tisch Cancer Center.

“By exploring combinations with Antibody-Drug Conjugates (ADCs) in the perioperative setting, we aim to improve survival expectations for people facing muscle-invasive bladder cancer.” — Dr. Marjorie Green, Head of Oncology, Global Clinical Development, Merck Research Laboratories.

Safety and Global Availability

The safety profile of the combination was consistent with previous trials, with no new safety signals identified. Merck, Pfizer, and Astellas plan to present the full data at an upcoming medical meeting and will submit the findings to global regulatory authorities for expanded approval.

Currently, the KEYTRUDA plus Padcev combination is already approved in several countries for metastatic urothelial cancer and for MIBC patients who cannot receive cisplatin. These new results could expand its use to virtually all eligible MIBC patients