Dr Gupta on Updated Data With Enfortumab Vedotin Plus Pembrolizumab in Urothelial Cancer

“With a median follow-up of approximately 2.5 years, we saw that the [survival] benefit [with enfortumab vedotin plus pembrolizumab] was maintained. The curves were still separated nicely. [Additionally], the median DOR was approximately 2 years…This is very promising.”

Shilpa Gupta, MD, director, Genitourinary Medical Oncology, Taussig Cancer Institute, co-leader, Genitourinary Oncology Program, Cleveland Clinic, discusses updated survival and response data from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) evaluating enfortumab vedotin-efjv (Padcev) plus pembrolizumab (Keytruda) in previously untreated locally advanced or metastatic urothelial cancer.

Shilpa Gupta, MD, director, Genitourinary Medical Oncology, Taussig Cancer Institute, co-leader, Genitourinary Oncology Program, Cleveland Clinic, discusses updated survival and response data from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) evaluating enfortumab vedotin-efjv (Padcev) plus pembrolizumab (Keytruda) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).

Updated findings from the EV-302/KEYNOTE-A39 trial (NCT04223856), which were presented during the 2025 Genitourinary Cancers Symposium, demonstrated durable efficacy with the combination and did not reveal any new safety signals. These data reinforce the role of enfortumab vedotin plus pembrolizumab as a first-line standard of care for patients with locally advanced or metastatic urothelial carcinoma, Gupta begins. This pivotal study previously demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits compared with chemotherapy, leading to a global change in treatment guidelines, she notes.

With an additional year of follow-up, bringing the median follow-up to approximately 2.5 years, the survival advantage achieved with enfortumab vedotin plus pembrolizumab was sustained, Gupta says. The median OS in the overall population was 33.8 months (95% CI, 26.1-39.3) vs 15.9 months (95% CI, 13.6-18.3) with the combination vs chemotherapy, respectively, (HR, 0.51; 95% CI, 0.43-0.61; nominal 2-sided P = .00001). The duration of response was 23.3 months (95% CI, 17.8-not evaluable). The Kaplan-Meier curves continued to show clear separation, indicating a durable benefit. These findings align with long-term data from phase 1/2 EV-103 (NCT03288545), which reinforced expectations for the durability of responses with the combination, she adds.

An exploratory analysis of patients with confirmed clinical complete responses (cCR) further supported the regimen’s effectiveness, Gupta continues. At 2 years, 74% of patients who achieved a cCR with enfortumab vedotin plus pembrolizumab remained in cCR, a substantial improvement compared with chemotherapy, she notes. Importantly, no new safety signals emerged with longer follow-up, underscoring the tolerability of the combination, she says.

These updated results provide additional confidence in the durability of enfortumab vedotin plus pembrolizumab in the first-line setting and further solidify its role as the preferred frontline regimen for patients with urothelial carcinoma, Gupta concludes.