Europe Expands Keytruda and Padcev Use in Bladder Cancer to All Patients Eligible for Surgery
Key Facts
The European Commission expanded approval of the Keytruda and Padcev regimen to adults with resectable muscle-invasive bladder cancer, regardless of their eligibility to receive cisplatin. The regimen is given before surgery, with treatment continuing after radical cystectomy, according to a Merck statement. The decision covers pembrolizumab, marketed as Keytruda, with enfortumab vedotin, marketed as Padcev. Approval was based on results from the phase 3 KEYNOTE-B15 trial, also known as EV-304. The study was conducted in collaboration with Pfizer and Astellas, but the approved products are Merck’s Keytruda and Padcev, according to the company statement.
Among patients eligible for cisplatin, the risk of an event in event-free survival fell by 47% with the combination regimen compared with chemotherapy before surgery followed by surgery. These events were recorded in 87 of 405 patients, or 21%, in the Keytruda and Padcev group, compared with 146 of 403, or 36%, in the chemotherapy group. The trial enrolled 808 patients and randomly assigned them in a 1:1 ratio to the two groups. Patients in the first group received the combination regimen, while the other group received gemcitabine and cisplatin before surgery. These results compare the two regimens in patients eligible for cisplatin, while the new European approval expands the approved population to include patients regardless of that eligibility.
The trial showed a 35% reduction in the risk of death in the combination therapy group compared with the chemotherapy group. There were 69 deaths among 405 patients, or 17%, with Keytruda and Padcev, compared with 99 of 403, or 25%, with chemotherapy. The pathological complete response rate was also 55.8% in the combination therapy group, versus 32.5% in the comparison group. EV-304 lead investigator Matthew Galsky said the regimen gives doctors an option that “meaningfully reduces the risk of recurrence and improves overall survival, without cisplatin-based chemotherapy.” The study defined event-free survival as a primary endpoint, while key secondary endpoints included overall survival and pathological complete response rate.
The efficacy measures came alongside a higher rate of severe side effects in the combination therapy arm. Grade 3 or higher side effects occurred in 75.7% of patients who received Keytruda and Padcev, compared with 67.2% in the chemotherapy group, according to data reported by OncLive. Against a backdrop of demand for additional treatment options, Astellas said just under half of cisplatin-eligible patients experience a disease recurrence within 5 years, despite preoperative chemotherapy followed by cystectomy being a standard approach. EV-304 included a randomized, controlled, open-label comparison of combination therapy before and after surgery against preoperative chemotherapy, with curative-intent cystectomy in both arms. Less than 6 months earlier, the EU approval of the regimen had covered the cisplatin-ineligible population; the new approval then expanded the target population.
The Commission’s approval does not mean the treatment will be commercially available immediately or at the same time in all European countries. Merck said the timing of availability in each country depends on multiple factors, including completion of national reimbursement procedures. Astellas added that it is working with regulatory authorities and health technology assessment bodies across the EU to support patient access following approval. On the company front, Astellas said it had already incorporated the impact of the approval into its financial forecasts for the current fiscal year ending March 31, 2027. The trial registry lists May 18, 2028, as the estimated study completion date, after the trial began on April 21, 2021, and participant enrollment was completed on October 27, 2025.