The increasingly more popular combination of Padcev and Keytruda has expanded its bladder cancer territory once again.
Thanks to an FDA nod on July 10, Padcev and Keytruda have become the first muscle-invasive bladder cancer (MIBC) treatment that do not require considerations over the patient’s eligibility for cisplatin-based chemotherapy.
The latest go-ahead allows the combo as neoadjuvant treatment before surgery, followed as adjuvant treatment after surgical removal of the bladder in MIBC, building on a previous perioperative indication that was limited to cisplatin-ineligible patients.
The inclusive MIBC label adds to the Padcev-Keytruda combo’s well-established profile in metastatic bladder cancer. It arrives more than a month earlier than the FDA’s target decision date of Aug. 17 under an already accelerated priority review timeline.
“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,” Aamir Malik, Pfizer’s chief U.S. commercial officer, said in a July 10 statement.
Pfizer and Astellas are partners on Padcev, a Nectin-4 antibody-drug conjugate. For Merck & Co.’s Keytruda, the PD-1 inhibitor can either be used in its original infusion or its subcutaneous formulation, Keytruda Qlex.
The companies have results from the EV-304 (Keynote-B15) trial to thank for the latest approval. In the phase 3 study, Padcev and Keytruda used both before and after surgery significantly lowered the risk of death by 35% compared with neoadjuvant chemotherapy alone in MIBC patients who are eligible for cisplatin-based chemo.
The combo also led to a 47% reduction in the risk of tumor recurrence, disease worsening or death versus presurgical gemcitabine with cisplatin. About 79.4% of patients who took the 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, meaning that they saw no sign of cancer in resected tissues, after receiving Padcev and Keytruda. Only 32.5% of those in the chemotherapy arm could say the same.
Before Friday’s approval, AstraZeneca’s PD-L1 inhibitor Imfinzi became the first immunotherapy to win a perioperative MIBC label in March of 2025. But because the Imfinzi regimen involves cisplatin, only patients eligible for the chemo can get it.
AZ’s go-head was based on the phase 3 Niagara trial, which linked the Imfinzi-chemo regimen to a 32% improvement in event-free survival and a 25% improvement in overall survival versus chemo. The pCR rate was 33.8% for Imfinzi, versus 25.8% for control.
Looking to secure its own cisplatin-agnostic label, AZ recently reported positive results from its phase 3 Volga trial in cisplatin-ineligible patients, although detailed data remain under wraps.
The split of MIBC subpopulations based on cisplatin eligibility is around 50-50.
Meanwhile, hoping to continue Padcev and Keytruda’s clinical winning streak and further expand the star combination’s reach, Astellas recently started EV-309, a phase 3 study for the combo for bladder-sparing MIBC, namely in patients whose cancer has not spread outside the bladder.
With increased penetration in first-line metastatic bladder cancer and early momentum in MIBC, Astellas reported Padcev sales of 221 billion Japanese yen ($1.37 billion) in its fiscal year 2025 which ended this March, good for a 35% increase year over year.