FDA Clears Immunotherapy Combination for Bladder Cancer
The U.S. Food and Drug Administration has approved the use of pembrolizumab (Keytruda) in combination with enfortumab vedotin-ejfv (Padcev) as a neoadjuvant treatment for adults with muscle-invasive bladder cancer (MIBC). This regimen, which includes subsequent adjuvant treatment following radical cystectomy, provides a new therapeutic option for patients who are eligible for cisplatin-based chemotherapy.
Trial Data Shows Survival Gains
Regulatory approval follows results from the phase 3, randomized KEYNOTE-B15/EV-304 trial. Researchers randomized 808 patients with previously untreated muscle-invasive bladder cancer to receive either the immunotherapy combination or standard neoadjuvant gemcitabine and cisplatin.
The immunotherapy group demonstrated a 47% improvement in event-free survival (EFS) and a 35% improvement in overall survival (OS). While the median EFS was not reached in the immunotherapy arm, the control group recorded a median EFS of 48.5 months.
Prescribing and Dosing Protocols
The regimen is intended for candidates undergoing radical cystectomy with pelvic lymph node dissection. Clinicians administer pembrolizumab at 200 mg intravenously every three weeks or 400 mg every six weeks for up to 24 months, or until disease progression or toxicity occurs.
Enfortumab vedotin-ejfv is administered at 1.25 mg/kg on days 1 and 8 of a 21-day cycle for four cycles during the neoadjuvant phase. Treatment continues for five cycles in the adjuvant phase, administered every three weeks alongside pembrolizumab. When both drugs are scheduled for the same day, clinicians must administer enfortumab vedotin-ejfv first.
Managing Toxicity and Side Effects
The FDA prescribing information warns of distinct toxicity profiles for both agents. Pembrolizumab carries risks of immune-mediated adverse reactions, infusion-related reactions, complications following allogeneic hematopoietic stem cell transplantation, and potential embryo-fetal toxicity.
Enfortumab vedotin-ejfv requires monitoring for severe skin reactions, hyperglycemia, pneumonitis, interstitial lung disease, peripheral neuropathy, ocular disorders, infusion site extravasation, and embryo-fetal toxicity.
A Shift in Standard Care
By utilizing immunotherapy before and after surgery, the protocol significantly extends the time patients remain free of disease progression or death, potentially improving long-term outcomes for those facing this diagnosis.