Astellas Pharma and Pfizer have announced positive topline results from a pivotal Phase 3 clinical trial showing that their combination therapy significantly improves survival for patients with muscle-invasive bladder cancer (MIBC), a disease where outcomes have long remained poor despite aggressive treatment.

 

The interim analysis of the EV-304 trial, also known as KEYNOTE-B15, found that PADCEV (enfortumab vedotin) combined with Keytruda (pembrolizumab) beat standard cisplatin-based chemotherapy when used before and after surgery in eligible patients. The study met its primary endpoint, delivering clinically meaningful and statistically significant gains in event-free survival, while also achieving a key secondary endpoint of improved overall survival.

 

The combination also outperformed chemotherapy on another important secondary endpoint: pathologic complete response. Patients receiving PADCEV plus pembrolizumab before surgery were significantly more likely to show no remaining evidence of cancer compared with those given neoadjuvant chemotherapy. The safety profile was consistent with what is already known for the regimen.

 

“Despite available treatment options, nearly half of patients with muscle-invasive bladder cancer progress to metastatic disease within three years of diagnosis. The EV-304 results represent a key milestone in the new era of urothelial cancer treatment. 

 

"Together, the EV-303 and EV-304 results show that perioperative enfortumab vedotin plus pembrolizumab can positively impact the treatment journey for patients with muscle-invasive bladder cancer, offering significant survival gains across cisplatin-ineligible and cisplatin-eligible patients, signaling a shift from conventional platinum-based chemotherapy and the potential to transform the standard of care,” said Christopher Hoimes, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute and an EV-304 principal investigator.

 

The findings build on recent momentum for the regimen, which has already received US approval for cisplatin-ineligible patients with MIBC.

 

“Building on the recent U.S. approval for cisplatin-ineligible patients living with MIBC, these positive EV-304 findings reinforce the potential of PADCEV plus pembrolizumab to improve survival outcomes for a broad population of patients living with muscle-invasive bladder cancer. 

 

"Together with the EV-303 data, these results strengthen the evidence supporting this combination regimen as a treatment option for patients regardless of cisplatin eligibility. We are committed to bringing forth much-needed advancements and hope to more patients,” said Moitreyee Chatterjee-Kishore, Head of Oncology Development at Astellas.

 

Pfizer executives said the data point to a possible turning point in how the disease is treated.

 

“For the first time, patients with muscle-invasive bladder cancer are seeing significant survival benefits from combination therapy in a perioperative setting without the need for platinum-based chemotherapy, signaling the potential for a new standard of care for this community. 

 

"The EV-304 results, combined with the recent unprecedented results from the EV-303 trial, showcase the promising future of this regimen as a cornerstone of care for bladder cancer regardless of cisplatin eligibility,” said Jeff Legos, Pfizer’s Chief Oncology Officer.

 

Bladder cancer is the ninth most common cancer worldwide.