When will you recommend enfortumab vedotin plus pembrolizumab as first-line treatment of metastatic urothelial carcinoma for cisplatin-ineligible patients?

This is a timely question given the US FDA approval of the pembro/EV combination on 4/3/2023. Currently, the label is for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. There are a variety of definitions for cisplatin ineligibility but the most commonly used one is the AUA/ASCO/ASTRO/SUO consensus definition provided here:

Baseline renal dysfunction with an estimated or calculated creatinine clearance < 60ml/min, althoug...

The enfortumab vedotin (EV) + pembrolizumab regimen received accelerated approval by the US FDA in April 2023 for cisplatin-ineligible patients with advanced urothelial carcinoma. The approval was based on cohorts A (Phase I/Ib) and K (randomized phase II comparison of EV vs. EV+pembrolizumab) of the EV103 trial. The confirmed ORR in 121 patients receiving EV+pembrolizumab in both cohorts was 68%, including 12% with complete responses. The median DoR for the dose escalation cohort + Cohort A was...