Padcev plus Keytruda significantly improves survival for certain patients with bladder cancer when given before, after surgery: Pfizer

Written By :  Ruchika Sharma
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2025-08-17 05:00 GMT   |   Update On 2025-08-17 05:00 GMT
Pfizer
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New York: Pfizer Inc. and Astellas Pharma Inc. have announced positive topline results from the Phase 3 EV-303 clinical trial (also known as KEYNOTE-905). The EV-303 study is evaluating PADCEV (enfortumab vedotin), a Nectin-4 directed antibody-drug conjugate, in combination with KEYTRUDA (pembrolizumab), a PD-1 inhibitor, as neoadjuvant and adjuvant treatment (before and after surgery) versus surgery alone, the current standard of care, in patients with muscle-invasive bladder cancer (MIBC) who are not eligible for or declined cisplatin-based chemotherapy.

At the first interim efficacy analysis, the trial demonstrated a clinically meaningful and statistically significant improvement in event-free survival (EFS), the study’s primary endpoint, and overall survival (OS), a key secondary endpoint, with neoadjuvant and adjuvant PADCEV plus KEYTRUDA versus surgery alone. An additional secondary endpoint of pathologic complete response (pCR) rate was also met.

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Christof Vulsteke, M.D., Ph.D., Head of Integrated Cancer Center Ghent (IKG, Belgium) and Clinical Trial Unit Oncology Ghent and EV-303 principal investigator said, “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. These EV-303 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.”

The trial is continuing to evaluate the secondary EFS, OS and pCR rate endpoints for neoadjuvant and adjuvant KEYTRUDA versus surgery alone as they continue to mature. The safety profiles for PADCEV plus KEYTRUDA and KEYTRUDA monotherapy were consistent with the known profiles of each treatment regimen.

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Head of Oncology Development, Astellas said, “These results from EV-303 represent a breakthrough for cisplatin-ineligible patients with muscle-invasive bladder cancer, demonstrating the potential of PADCEV in combination with KEYTRUDA when used before and after surgery as a new standard of care. We look forward to presenting further details on these data at an upcoming medical congress.”

Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 patients each year globally. MIBC represents approximately 30% of all bladder cancer cases. The standard treatment for patients with MIBC is neoadjuvant cisplatin-based chemotherapy followed by surgery, which has been shown to prolong survival.ii However, up to half of patients with MIBC are not eligible to receive cisplatin and face limited treatment options, typically undergoing surgery alone. 

Johanna Bendell, M.D., Oncology Chief Development Officer, Pfizer said, “PADCEV plus KEYTRUDA has already changed the treatment paradigm for patients with locally advanced or metastatic urothelial cancer as standard of care. These latest results underscore the practice-changing potential of this combination in earlier stages of bladder cancer, where it has the potential to improve outcomes for even more patients. Thank you to the patients and investigators who participated in this trial.”

Results will be submitted for presentation at an upcoming medical congress and will be discussed with global health authorities for potential regulatory filings. Neoadjuvant and adjuvant PADCEV plus KEYTRUDA is also being evaluated in cisplatin-eligible patients with MIBC in the EV-304 Phase 3 clinical trial (also known as KEYNOTE-B15).

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