Pune, India | November 24, 2025
The U.S. Food and Drug Administration (FDA) has approved the combination of pembrolizumab (Keytruda) and enfortumab vedotin-ejfv (Padcev) to treat adults with muscle-invasive bladder cancer (MIBC) who cannot undergo cisplatin chemotherapy. Clinicians can administer this regimen both before and after surgery, offering new hope for patients with limited treatment options.
In the pivotal KEYNOTE-905/EV-303 trial, researchers enrolled 344 patients with cisplatin-ineligible MIBC. Participants received Keytruda and Padcev as neoadjuvant therapy before radical cystectomy and pelvic lymph node dissection. After surgery, they continued adjuvant therapy to lower the risk of cancer recurrence. Regular treatment checkpoints ensured care was tailored to each patient’s risk profile.
The trial showed substantial clinical benefits. Event-free survival (EFS) improved significantly for patients receiving both drugs compared to surgery alone. The median EFS was not reached in the combination group, while the surgery-only group had a median EFS of 15.7 months. The hazard ratio of 0.40 underscored the therapy’s advantage. Overall survival (OS) also favored the combination; median OS was not reached for patients on both drugs, compared to 41.7 months in the control group, with a hazard ratio of 0.50. These results highlight meaningful survival gains for patients who previously faced poor prognoses.
Safety analyses showed that the regimen has a manageable risk profile, consistent with prior reports for pembrolizumab and enfortumab vedotin. Patients sometimes experienced immune-mediated side effects or infusion-related reactions. Enfortumab vedotin occasionally caused dermatologic issues, hyperglycemia, lung inflammation, peripheral neuropathy, ocular problems, or local infusion-site reactions. Most adverse events were controllable with monitoring and dosage adjustments, allowing clinicians to maintain treatment continuity. Careful postoperative attention helped address emerging symptoms and complications early.
The FDA approval defines a clear treatment schedule. During the neoadjuvant phase, patients receive pembrolizumab 200 mg intravenously every three weeks and enfortumab vedotin 1.25 mg/kg (up to 125 mg) on Days 1 and 8 of each 21-day cycle for three cycles. After surgery, enfortumab vedotin continues every three weeks for six cycles alongside pembrolizumab. Clinicians then give pembrolizumab alone, either 200 mg every three weeks for 14 cycles or 400 mg every six weeks for seven cycles. When they administer both drugs on the same day, they should give pembrolizumab after enfortumab vedotin to optimize efficacy and reduce adverse effects.
Regulatory pathways accelerated the approval. Project Orbis promoted global collaboration, while the FDA’s Assessment Aid sped up the review without compromising safety or effectiveness. Fast-tracking this therapy demonstrates growing support for early access to promising treatments, especially for high-risk patients whose needs are unmet by conventional approaches.
Experts consider this approval transformative for MIBC care. Many view the combination as a new clinical benchmark. This potentially improves survival and outcomes for patients previously underserved by standard therapies. The FDA advises healthcare professionals to promptly report severe reactions via MedWatch, as ongoing monitoring safeguards patient health and informs future strategies.
Ultimately, the FDA’s decision represents a major milestone in bladder cancer treatment. Combining immunotherapy with targeted therapy allows clinicians to address unmet needs and optimize care before and after surgery. With proper oversight and careful transitions between treatment phases, patients gain renewed hope for longer, healthier lives. This approval redefines what is possible in managing bladder cancer.
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