KEYTRUDA® and Padcev® Boost Survival for MIBC Cisplatin-Eligible Pre/Post Surgery

Merck recently announced promising results from the Phase 3 KEYNOTE-B15 trial, which evaluated the effectiveness of KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab vedotin-ejfv) for patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. This combination therapy showed significant improvements in event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rates compared to traditional neoadjuvant chemotherapy followed by surgery.

KEYNOTE-B15 Trial Overview

The KEYNOTE-B15 trial, also referred to as EV-304, is an open-label, randomized study designed to assess the combination of KEYTRUDA and Padcev as a perioperative treatment. Conducted in collaboration with Pfizer and Astellas, the trial involved 808 enrolled patients diagnosed with MIBC. Participants were randomly assigned to receive either:

• Four cycles of neoadjuvant KEYTRUDA plus Padcev followed by surgery, then 13 cycles of Keytruda and five cycles of Padcev after surgery.
• Four cycles of standard neoadjuvant chemotherapy (gemcitabine plus cisplatin) followed by surgery.

Results and Implications

The results demonstrated that the combination of KEYTRUDA and Padcev offered substantial benefits in patient outcomes. Dr. Matthew Galsky, a principal investigator, highlighted the importance of addressing recurrence risks in patients despite recent advancements in treatment options. He expressed optimism that the combination therapy could significantly enhance survival rates for MIBC patients.

Dr. Marjorie Green emphasized the need to make treatment decisions earlier in the disease process, suggesting that this could change the trajectory of cancer treatment for MIBC. The study’s findings reinforce the potential effectiveness of incorporating KEYTRUDA into earlier cancer care stages.

Safety Profile of the Combination Therapy

The safety profile observed in this trial was consistent with those previously established for both KEYTRUDA and Padcev, with no new safety concerns reported. The companies plan to engage with regulatory authorities globally regarding potential filings and will present the comprehensive data at future medical meetings.

Current Approvals and Ongoing Research

Currently, KEYTRUDA plus Padcev holds approval for treating adults with locally advanced or metastatic urothelial cancer in various regions, including the U.S. and the European Union. Additionally, it is cleared for patients with MIBC who cannot undergo cisplatin-based chemotherapy.

Merck continues to explore multiple ongoing clinical trials that evaluate KEYTRUDA across various stages of bladder cancer. Two key Phase 3 studies, KEYNOTE-866 and KEYNOTE-992, are focused on MIBC.

Conclusion

As research evolves, Merck remains committed to enhancing cancer treatment through innovative therapies like KEYTRUDA and Padcev. The promising results from the KEYNOTE-B15 trial could potentially reshape treatment landscapes for patients with muscle-invasive bladder cancer, effectively boosting survival rates and providing new hope for those facing this aggressive disease.