PADCEV plus Keytruda secures US FDA approval as neoadjuvant and adjuvant treatment for muscle-invasive bladder cancer irrespective of cisplatin eligibility

Pfizer and Astellas Pharma have announced that the US Food and Drug Administration has approved PADCEV (enfortumab vedotin-ejfv), a Nectin-4 directed antibody-drug conjugate, in combination with the PD-1 inhibitor Keytruda (pembrolizumab) or Keytruda QLEX (pembrolizumab and berahyaluronidase alfa-pmph), as a neoadjuvant and adjuvant treatment for adults with muscle-invasive bladder cancer regardless of their cisplatin eligibility. The approval marks the first platinum-free regimen to receive clearance for this patient population across all cisplatin eligibility groups.

The decision builds on the pivotal Phase 3 EV-304 clinical trial, presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium, and extends a prior November 2025 approval of the same combination as neoadjuvant and adjuvant treatment in cisplatin-ineligible patients, which had been grounded in the EV-303 Phase 3 trial published in the New England Journal of Medicine.

“For muscle-invasive bladder cancer, a comprehensive treatment approach is important; the neoadjuvant phase can help shrink the tumor and target undetectable cancer cells early before surgery, while the adjuvant phase can be critical in eliminating residual, undetectable cancer cells following surgery. These data from EV-304 and this approval show that by delivering this regimen across both the neoadjuvant and adjuvant phases, without platinum-based chemotherapy, we can significantly reduce the risk of recurrence and improve overall survival, offering a potential new standard of care for adult patients with muscle-invasive bladder cancer,” said Christopher Hoimes, DO, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute, and EV-304 Principal Investigator.

“Today’s approval marks a historic turning point for the treatment of muscle-invasive bladder cancer, providing adult patients with the first approved platinum-free combination regimen shown to significantly improve survival over the current standard of care, regardless of cisplatin-eligibility. PADCEV plus pembrolizumab has established itself as the standard of care for first line therapy of advanced stages of bladder cancer, and we’re thrilled to be able to provide this community a much-needed new treatment option in an earlier, potentially curative-intent setting,” said Aamir Malik, Executive Vice President and Chief US Commercial Officer, Pfizer.

“The approval of neoadjuvant and adjuvant PADCEV plus pembrolizumab expands the established impact of this combination and represents a critical leap forward in how muscle-invasive bladder cancer can be treated. By delivering a clinically meaningful survival benefit, with profound event-free survival and pathological complete response rates, this regimen is the first platinum-free treatment option in nearly 25 years to outperform standard of care chemotherapy, offering new hope to patients living with this disease,” said Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas.

Within the EV-304 trial, participants were assigned to receive surgery alongside either neoadjuvant and adjuvant PADCEV plus pembrolizumab or neoadjuvant chemotherapy. The PADCEV and pembrolizumab combination was delivered across a planned total of nine cycles of PADCEV and seventeen cycles of pembrolizumab, split between the pre and post-surgical periods. Against standard of care neoadjuvant gemcitabine and cisplatin, the combination delivered a 47% reduction in the risk of tumour recurrence, progression, or death, with an estimated 79.4% of patients remaining event-free at two years compared to 66.2% in the chemotherapy group. The risk of death fell by 35% relative to neoadjuvant chemotherapy. A pathological complete response was achieved in 55.8% of patients receiving the combination at the time of surgery, against 32.5% among those on chemotherapy. The safety profile remained consistent with earlier experience of this combination, and no new signals of concern emerged. Grade 3 or higher adverse events of any cause were recorded in 75.7% of those on neoadjuvant and adjuvant PADCEV plus pembrolizumab, compared to 67.2% in the neoadjuvant chemotherapy group.

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Related Topics and Keywords

bladder cancer, KEYTRUDA, muscle-invasive bladder cancer, neoadjuvant, padcev