Padcev/Keytruda Combo Extends Survival in Muscle-Invasive Bladder Cancer

Treatment with Padcev (enfortumab vedotin) plus Keytruda (pembrolizumab) demonstrated clinically meaningful and statistically significant improvements in event-free survival and overall survival in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC), according to data from an interim analysis of the phase 3 EV-304 trial (also known as KEYNOTE-B15).

Based on these data, which were shared in a news release from Astellas Pharma Inc., the trial met its primary end point. Additionally, the trial met key secondary end points, such as improvement in pathologic complete response rate with Padcev and Keytruda. This means that, when patients underwent surgery, a higher percentage of those treated with the combination had no detectable cancer remaining in the surgical specimen.

Moreover, safety outcomes for the combination matched what has already been established for Padcev plus Keytruda. No new safety concerns emerged in the review, indicating that the treatment profile remained predictable and consistent.

“For the first time, patients with MIBC 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,” Jeff Legos, chief oncology officer at Pfizer, said in the news release. “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.”

It was also emphasized in the news release that Padcev and Keytruda is the first and only regimen without platinum-based chemotherapy to these survival outcomes in cisplatin-eligible patients with MIBC when used before and after surgery.

How the EV-304 Trial Tested Padcev plus Keytruda in Muscle-Invasive Bladder Cancer

The EV-304 study evaluated Padcev plus Keytruda as both a neoadjuvant treatment, meaning before surgery, and an adjuvant treatment, meaning after surgery. Patients in this trial were eligible for cisplatin-based chemotherapy and were randomized to receive either standard therapy consisting of gemcitabine and cisplatin or Padcev plus Keytruda.

The clinical trial is a randomized, international phase 3 study comparing two treatment plans before and after surgery. Patients were assigned to either Padcev plus Keytruda or to chemotherapy using gemcitabine and cisplatin. All participants were scheduled for surgical removal of the bladder.

Researchers focused on whether the combination could prevent recurrence or spread in the period before and after surgery. They also assessed overall survival, the length of time patients remained alive, and complete response rates in surgical pathology samples.

The primary goal of this trial, event-free survival, was measured from the time patients entered the trial until progression prevented surgery, cancer recurrence after surgery, or death. Overall survival was a major secondary goal of the research.

Why MIBC Has High Recurrence Risk and Limited Treatment Options

MIBC is a serious condition often requiring multiple forms of therapy, the news release explains. Even when patient’s complete surgery, half experience recurrence. Many individuals cannot receive cisplatin-based chemotherapy due to health concerns, and those who do may still face high recurrence risk. It is due to this unmet need within the MIBC treatment landscape that study investigators launched the EV-304 clinical trial.

“Despite available treatment options, nearly half of patients with MIBC progress to metastatic disease within three years of diagnosis,” Christopher Hoimes, director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute, and EV-304 principal investigator, explained in the news release.

“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 Padcev plus Keytruda can positively impact the treatment journey for patients with MIBC, 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,” he continued.

Regulatory Path Ahead for Padcev plus Keytruda in MIBC

Padcev plus Keytruda is not currently approved for neoadjuvant and adjuvant treatment of cisplatin-eligible MIBC, the news release emphasizes. However, the company reported plans to present the EV-304 findings at an upcoming medical meeting and discuss the results with global health authorities to support potential regulatory submissions.

This news follows recent regulatory approval of Keytruda or Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) with Padcev for patients who are not eligible for cisplatin-based chemotherapy. That approval was based on the EV-303 study, which demonstrated notable survival benefit in that patient group. The new EV-304 data expand those findings to individuals who are able to receive cisplatin, indicating that this combination may offer advantages across a broad range of 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 Keytruda to improve survival outcomes for a broad population of patients living with MIBC,” Moitreyee Chatterjee-Kishore, head of Oncology Development at Astellas, concluded in the press release. “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.”

References

1. “PADCEV™ Plus Keytruda® Significantly Improves Survival for Patients with Muscle-Invasive Bladder Cancer Regardless of Cisplatin Eligibility,” by Astellas Pharma Inc. News release; Dec. 17, 2025.
2. FDA Approves Keytruda and Padcev for Muscle Invasive Bladder Cancer, by Spencer Feldman. CURE; Nov. 21, 2025. https://www.curetoday.com/view/fda-approves-keytruda-and-padcev-for-muscle-invasive-bladder-cancer

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