Dr Bedke on Enfortumab Vedotin Plus Pembrolizumab in Urothelial Carcinoma

“There was a pronounced benefit with enfortumab vedotin plus pembrolizumab compared with platinum-based chemotherapy [in patients with previously untreated urothelial cancer]. There was no specific subgroup [for whom] you should decide not to use enfortumab vedotin plus pembrolizumab.”

Jens Bedke, MD, a senior consultant in the Department of Urology & Transplantation Surgery at the Eva Mayr-Stihl Cancer Center Stuttgart, Klinikum Stuttgart, discussed findings from subgroup analyses of the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), which evaluated enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) vs chemotherapy alone in patients with untreated locally advanced or metastatic urothelial cancer.

Results presented during the 2025 ASCO Annual Meeting showed that enfortumab vedotin plus pembrolizumab generated superior progression-free survival (PFS), overall survival (OS), and overall response rates (ORR) compared with chemotherapy across all prespecified subgroups of interest, Bedke began. Subgroups included patients with upper tract and lower tract disease, lymph node–only metastases, visceral metastases, and liver metastases, he continued. Therefore, enfortumab vedotin plus pembrolizumab should be considered regardless of patient subgroup classification, he asserted.

The median PFS among patients with primary disease in the upper tract in the investigational (n = 135) and chemotherapy (104) arms was 12.3 months (95% CI, 7.6-16.4) and 6.2 months (95% CI, 6.1-6.9), respectively (HR, 0.542; 95% CI, 0.384-0.763). Patients with visceral metastases in the investigational (n = 318) and control (n = 318) arms achieved a median PFS of 10.4 months (95% CI, 8.3-12.7) and 6.2 months (95% CI, 6.0-6.3), respectively (HR, 0.477; 95% CI, 0.393-0.579).

The respective median PFS values among those with lymph node–only metastases in the investigational (n = 103) and control (n = 104) arms were 22.1 months (95% CI, 15.3-not evaluable) and 8.3 months (95% CI, 6.2-13.1; HR, 0.473; 95% CI, 0.317-0.704). Patients with liver metastases in the investigational (n = 100) and control (n = 99) arms had a median PFS of 8.1 months (95% CI, 6.1-12.0) and 6.0 months (95% CI, 4.4-6.3), respectively (HR, 0.548; 95% CI, 0.392-0.766).

Bedke noted that the benefit achieved with the enfortumab vedotin combination was particularly notable in patients with lymph node–only metastases. These patients achieved a complete response rate of 50% and an ORR of 77.5% with enfortumab vedotin plus pembrolizumab, he concluded.