Jens Bedke, MD, on efficacy of EV plus pembrolizumab across subgroups in la/mUC

The phase 3 EV-302 trial (NCT04223856) showed that the combination of enfortumab vedotin plus pembrolizumab (EV+P) extended overall survival (OS) and progression-free survival (PFS) compared with chemotherapy in patients with locally advanced/metastatic urothelial carcinoma. These data supported the FDA approval of EV+P in December 2023 and established the combination as the standard of care in this setting.

Data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois shed light on the long-term efficacy of this combination across pre-specified subgroups in the trial.¹ These stratifications includedprimary disease site of origin (upper and lower tracts), lymph node (LN)–only disease, and presence of liver metastases (present and absent).

Overall, EV+P demonstrated superior efficacy over chemotherapy across all specified subgroups. In an interview at ASCO, presenting author Jens Bedke, MD, walked through the key takeaways from these findings.

Bedke explained, “I think the important message is that we have no specific subgroup which will have a more pronounced benefit of EV+P if compared to the platinum-based chemotherapy. Selecting patients for EV+P is not based on the site of the metastasis, lymph nodes, liver mets, upper tract, lower tract. This is not a treatment selector for EV+P, because EV+P is superior in terms of PFS, OS, and response rate compared to platinum-based chemotherapy.”

According to Bedke, treatment selection should involve a conversation between the treating physician and the patient on the risks and benefits of EV+P.

“We all know in the clinical setting, it's a judgment, together with the patient, of you should go for this therapy, acknowledging the risk/harm [to] benefit ratio. To balance that, the risk and the benefit are much more pronounced for the benefit side in terms of the efficacy.” 

REFERENCE

1. Bedke J, Powles T, Valderrama B, et al. EV-302: Long-term subgroup analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). J Clin Oncol. 2025. doi:10.1200/JCO.2025.43.16_suppl.4571