The US Food and Drug Administration has approved pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex), each with enfortumab vedotin-ejfv (Padcev), as neoadjuvant treatment followed by adjuvant therapy for adults with muscle-invasive bladder cancer who are candidates for cystectomy. The approval epands the prior indication from patients who were ineligible for cisplatin to all adults with muscle-invasive bladder cancer who are candidates for cystectomy.
The approval is based on results from the KEYNOTE-B15/EV-304 trial, an open-label, randomized, active-controlled, multicenter study that enrolled 808 patients with previously untreated muscle-invasive bladder cancer who were eligible for cisplatin-based chemotherapy and were candidates for radical cystectomy with pelvic lymph node dissection. Researchers randomly assigned patients to receive neoadjuvant pembrolizumab plus enfortumab vedotin-ejfv followed by surgery and adjuvant treatment with the same regimen or neoadjuvant gemcitabine plus cisplatin followed by surgery.
The primary efficacy endpoint was event-free survival, with overall survival serving as an additional efficacy endpoint. Median event-free survival was not reached in the pembrolizumab combination group and was 48.5 months in the gemcitabine plus cisplatin group. Median overall survival was not reached in either treatment group.
According to the FDA, the safety profile of pembrolizumab plus enfortumab vedotin-ejfv was consistent with that observed in prior trials of the combination in urothelial cancer. Pembrolizumab prescribing information includes warnings regarding immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. Enfortumab vedotin-ejfv prescribing information includes warnings regarding skin reactions, hyperglycemia, pneumonitis or interstitial lung disease, peripheral neuropathy, ocular disorders, infusion site extravasation, and embryo-fetal toxicity.
The FDA reviewed the application under Project Orbis in collaboration with the following regulatory agencies: Australian Therapeutic Goods Administration, Health Canada, Switzerland's Swissmedic, the United Kingdom's Medicines and Healthcare products Regulatory Agency, and the Israel Ministry of Health. The application received priority review, and the FDA approved it 5 weeks before the agency's goal date.
Source: US Food and Drug Administration
