Keytruda and Padcev Generate Positive Topline Findings in Bladder Cancer

Keytruda and Padcev generated promising topline results for those with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy.

Keytruda (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv) generated promising topline results in patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy, according to a news release from Merck which shared the data which was generated by the phase 3 KEYNOTE-905 trial (also known as EV-303).

The combination, when given both before and after radical cystectomy surgery, demonstrated a statistically significant and clinically meaningful improvement in event-free survival, as well as overall survival and pathologic complete response rate compared with surgery alone.

Notably, these phase 3 results mark the first positive outcomes for a systemic therapy shown to improve survival when given before and after surgery in patients who are ineligible for cisplatin-based chemotherapy, representing a significant advancement, according to the news release.

“Patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy have not seen any treatment advance beyond surgery and face high rates of disease recurrence and a poor prognosis, even after having their bladder removed,” said KEYNOTE-905 principal investigator, Dr. Christof. “The KEYNOTE-905 study results mark the first time a systemic treatment approach, used before and after surgery, significantly extended survival over standard-of-care surgery in this population, demonstrating the potential of this combination to address a critical unmet need.”

Vulsteke is the head of Integrated Cancer Center Ghent (IKG) and Clinical Trial Unit Oncology Ghent.

The companies intend to share these findings with regulatory authorities worldwide and plan to present the results at an upcoming medical meeting.

Breaking Down the KEYNOTE-905 Trial

KEYNOTE-905 is an open-label, randomized, multi-arm, controlled trial evaluating Keytruda, with or without Padcev, given both before and after surgery, compared with surgery alone in patients with muscle-invasive bladder cancer who are either ineligible for or have declined cisplatin-based chemotherapy.

A total of 595 patients were randomly treated one of three arms:

• Arm A received three cycles of preoperative Keytruda followed by radical cystectomy and 14 cycles of postoperative Keytruda.
• Arm B underwent surgery alone.
• Arm C received three cycles of preoperative Keytruda plus Padcev, followed by radical cystectomy, then six cycles of postoperative Keytruda plus Padcev and eight additional cycles of Keytruda alone.

This trial builds on the clinical benefit of combining Keytruda with Padcev in patients with locally advanced or metastatic urothelial cancer and remains ongoing to evaluate the outcomes for the comparisons between arm A and arm B.

Additionally, the safety findings for Keytruda combined with Padcev were consistent with the established safety profiles of each therapy. No new safety concerns emerged from the combination.

The Future of Treatment with Keytruda and Padcev

It is also important to note that the Keytruda and Padcev combination is already approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer in the United States, the European Union, Japan, as well as several other countries internationally. When used as a monotherapy, Keytruda is approved for patients with locally advanced or metastatic urothelial cancer and non-muscle-invasive bladder cancer across the United States, the European Union, Japan, and other countries.

Additional phase 3 trials are underway and are aiming to evaluate Keytruda in all stages of bladder cancer, including non-muscle-invasive, muscle-invasive, and metastatic disease. Three of these trials focus on muscle-invasive bladder cancer (the KEYNOTE-866 clinical trial; the KEYNOTE-992 study, and the KEYNOTE-B15 trial [also referred to as EV-304]).

In non-muscle-invasive bladder cancer, Keytruda is being studied in combination with Bacillus Calmette-Guerin (BCG) in a phase 3 study (the KEYNOTE-676 trial). Additionally, Keytruda is being investigated as adjuvant therapy for patients with localized muscle-invasive urothelial carcinoma and locally advanced urothelial carcinoma in another phase 3 trial (the KEYNOTE-123 study).

“There is a real and pressing need for more effective options for patients with bladder cancer who are ineligible for cisplatin-based treatment,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “The compelling survival results observed in this study reinforce the potential of combining Keytruda with an antibody-drug conjugate to help address a significant unmet need in this vulnerable population.”

Reference

1. “Keytruda® (pembrolizumab) plus Padcev® (enfortumab vedotin-ejfv) Significantly Improved Event-Free and Overall Survival and Pathologic Complete Response Rate for Certain Patients with Muscle-Invasive Bladder Cancer When Given Before and After Surgery,” by Merck. News release. August 12, 2025.

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