Medical Professionals Reference (MPR)Padcev Plus Keytruda Approved as First-Line Treatment for Urothelial Cancer

Demonstrating compelling efficacy in the EV-103 trial, the combination of enfortumab vedotin-ejfv and pembrolizumab emerges as a promising treatment for patients with locally advanced or metastatic urothelial carcinoma ineligible for cisplatin-based chemotherapy.

The recent approval of enfortumab vedotin-ejfv in combination with pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who are ineligible for cisplatin-based chemotherapy was substantiated by compelling results from the multi-cohort Phase 1b/2 EV-103 trial. In the dose escalation cohort and cohort A of the trial, patients received this innovative combination therapy. In cohort K, patients were randomized to receive either the combination or enfortumab vedotin-ejfv monotherapy. The main efficacy outcome measures were the objective response rate (ORR) and duration of response (DOR), with the ORR reaching 68% (95% CI, 58.7-76.0) among the 121 patients who received the combination therapy. Moreover, the median DOR was reported as 22.1 months for the dose escalation and cohort A.

Nevertheless, patients did report a range of adverse reactions, most commonly increased glucose, increased aspartate aminotransferase, rash, and decreased hemoglobin, among others. The approval of this therapy is dependent on the validation and depiction of clinical benefits from the ongoing Phase 3 EV-302 confirmatory trial. Given the promising ORR and DOR, the combination of enfortumab vedotin-ejfv and pembrolizumab could revolutionize the treatment of patients with la/mUC who are ineligible for cisplatin-based chemotherapy, providing a viable new therapeutic approach for this patient population.