Dr Gupta on Responses With Enfortumab Vedotin/Pembrolizumab in Urothelial Carcinoma

“The median duration of response was [23.3 months], which is reassuring. In patients with a [confirmed] complete responses, 74.3% of patients remained in complete response at 2 years.”

Shilpa Gupta, MD, the director of Genitourinary Medical Oncology at the Taussig Cancer Institute and the coleader of the Genitourinary Oncology Program in the Department of Hematology and Medical Oncology at the Cleveland Clinic, discussed response and subgroup data with enfortumab vedotin-efjv (Padcev) plus pembrolizumab for the treatment of patients with untreated locally advanced or metastatic urothelial carcinoma.

Findings from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), which were presented during the 2025 Genitourinary Cancers Symposium, revealed that the median duration of response (DOR) was 23.3 months (95% CI, 17.8-not evaluable [NE]) among patients who responded to the combination (n = 295), Gupta began. Comparatively, the median DOR among responders in the chemotherapy control arm (n = 195) was 7.0 months (95% CI, 6.2-9.0). The 12- and 24-month DOR rates in the combination arm were 67.5% and 49.4%, respectively. These rates were 35.1% with enfortumab vedotin and 24.0% in the chemotherapy arm.

Moreover, Gupta noted that a significant portion of patients who received the combination achieved a sustained complete response (CR). Specifically, patients who had a CR in the combination arm (n = 133) experienced a 24-month duration of CR (DOCR) rate of 74.3%, she emphasized. The median DOCR was not reached (95% CI, NE-NE) and the 12-month DOCR rate was 84.3%. In the chemotherapy arm, patients who achieved a CR (n = 64) had a median DOCR of 15.2 months (95% CI, 10.3-NE); the 12- and 24-month DOCR rates were 60.0% and 43.2%, respectively.

Enfortumab vedotin in combination with pembrolizumab also produced a consistent benefit vs chemotherapy in terms of overall survival (OS) across prespecified patient subgroups, Gupta explained. The OS benefit was maintained irrespective of the presence of visceral metastases, metastatic site, or cisplatin eligibility, she concluded.