The FDA has approved the Padcev and Keytruda combination as the first platinum-free regimen for adult patients with muscle-invasive bladder cancer, regardless of cisplatin eligibility.
The landmark approval marks a significant territorial expansion for the increasingly popular combo, which has been building momentum across multiple bladder cancer settings over recent years.
The decision was based on results from the pivotal Phase 3 EV-304 clinical trial, also known as KEYNOTE-B15, which were presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium.
The combination delivered a 47% reduction in the risk of tumour recurrence, disease worsening or death compared with presurgical gemcitabine with cisplatin chemotherapy.
Approximately 79.4% of patients on the Padcev-Keytruda regimen were estimated to be free of those negative disease developments at two years, versus 66.2% for those in the control arm.
At the time of surgery, 55.8% of patients achieved a pathological complete response after receiving the combination, meaning no sign of cancer was detected in resected tissues following treatment.
By comparison, only 32.5% of patients in the chemotherapy arm achieved the same outcome, underlining the substantial clinical difference between the two approaches.
AstraZeneca’s (AZN) PD-L1 inhibitor Imfinzi had previously become the first immunotherapy to win a perioperative muscle-invasive bladder cancer label in March 2025, but that regimen requires cisplatin, limiting its eligible patient pool.
In the Niagara trial supporting Imfinzi’s approval, the drug recorded a pathological complete response rate of 33.8%, versus 25.8% in the comparison group, figures that trail the newer Padcev-Keytruda data.
Merck & Co.’s (MRK) Keytruda, paired with Padcev, already received a first-in-disease perioperative nod in cisplatin-ineligible muscle-invasive bladder cancer in November, and a separate EV-304 readout has placed the combo under FDA priority review for the cisplatin-eligible setting, with a target action date of 17 August 2026.
Astellas recently initiated EV-309, a Phase 3 study examining the Padcev and Keytruda combination for bladder-sparing muscle-invasive bladder cancer in patients whose cancer has not spread outside the bladder.
Astellas reported Padcev sales of 221 billion Japanese yen, equivalent to approximately $1.37 billion, in its fiscal year 2025, which ended this March, reflecting the drug’s growing commercial footprint.