Dr Powles on the Efficacy of Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Cancer

Thomas Powles, MD, MBBS, MRCP, professor, urology, the University of London; director, Barts Cancer Centre, United Kingdom, discusses the safety and efficacy of enfortumab vedotin-ejfv (Padcev) with pembrolizumab (Keytruda) based on data from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) in patients with previously untreated, locally advanced or metastatic urothelial carcinoma.

The global, open-label, randomized trial randomly assigned 886 patients who were eligible for cisplatin- or carboplatin-containing chemotherapy in a 1:1 ratio to either the combination or standard chemotherapy. The study population was representative of the real-world urothelial cancer population, with both arms well-balanced in terms of visceral metastasis, eligibility for cisplatin-based therapy, and ECOG performance status.

Results from the study were presented at the 2023 ESMO Congress, showing that enfortumab vedotin plus pembrolizumab elicited statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) vs chemotherapy, as well as demonstrated a tolerable safety profile in patients, Powles reports. At a median follow-up of 17.2 months, patients achieved a 55% reduction in the risk of disease progression (hazard ratio [HR], 0.45) and 53% reduction in the risk of death (HR, 0.47) with the combination vs chemotherapy, he details. The median PFS was 12.5 months (95% CI, 10.4-16.6) with the combination vs 6.3 months (95% CI, 6.2-6.5) with chemotherapy. Furthermore, the median OS was 31.5 months (95% CI, 25.4-not reached) vs 16.1 months (95% CI, 13.9-18.3) with enfortumab vedotin/pembrolizumab and chemotherapy, respectively.

These results showcase a significant advancement in urothelial cancer, as first-line chemotherapy had not previously been surpassed in an unselected clinical trial population, Powles notes. The combination also exhibited high responses, including a 67.7% overall response rate and an 29.1% complete response rate, Powles states. Notably, the median duration of response was not reached with the combination, he adds. Overall, these practice-changing findings support the use of enfortumab vedotin plus pembrolizumab as a new standard of care in urothelial cancer, Powles concludes.