Breakthrough in Bladder Cancer Treatment: Padcev-Keytruda Combo Shows Promise in Phase 3 Trial

Pfizer, Astellas, and Merck have announced groundbreaking results from a phase 3 clinical trial evaluating the combination of Padcev (enfortumab vedotin) and Keytruda (pembrolizumab) in muscle-invasive bladder cancer (MIBC) patients ineligible for cisplatin-based chemotherapy. The study, known as EV-303 or Keynote-905, demonstrated significant improvements in survival outcomes when the drug combination was administered before and after radical cystectomy surgery.

Unprecedented Efficacy in Cisplatin-Ineligible MIBC Patients

The Padcev-Keytruda combination achieved a statistically significant and clinically meaningful improvement in event-free survival compared to surgery alone. Additionally, the drug duo met its secondary endpoints of overall survival and pathologic complete response rate. This marks the first positive phase 3 study to improve survival in cisplatin-ineligible MIBC patients, a population with limited treatment options.

Dr. Johanna Bendell, Pfizer's oncology chief development officer, emphasized the "practice-changing potential" of the combination therapy in earlier stages of bladder cancer. Dr. Moitreyee Chatterjee-Kishore, head of oncology development at Astellas, described the results as a "breakthrough" that could establish a new standard of care for this patient group.

Expanding the Reach of Immunotherapy in Bladder Cancer

The success of the Padcev-Keytruda combination builds upon its previous achievements in advanced bladder cancer. In 2022, the duo received broad FDA approval for first-line treatment of locally advanced or metastatic urothelial cancer, demonstrating a 53% reduction in the risk of death compared to chemotherapy.

The current study focuses on MIBC, which accounts for 30% of all bladder cancer cases. Up to half of MIBC patients are ineligible for the standard cisplatin-based chemotherapy, underscoring the critical need for alternative treatment options.

Future Implications and Ongoing Research

The companies plan to discuss these results with regulatory authorities worldwide and present them at an upcoming medical meeting. A parallel study, EV-304 or Keynote-B15, is evaluating the Padcev-Keytruda combination in cisplatin-eligible MIBC patients.

Pfizer, which acquired Padcev through its $43 billion Seagen buyout, stands to benefit significantly from these positive results. Astellas has projected peak sales for Padcev to reach between 400 billion to 500 billion Japanese yen ($2.7 billion to $3.4 billion).

As the landscape of bladder cancer treatment continues to evolve, the Padcev-Keytruda combination represents a promising advance in the field of immuno-oncology, potentially offering new hope to patients with limited therapeutic options.