Dr Gupta on the Efficacy of Enfortumab Vedotin Plus Pembrolizumab in Urothelial Carcinoma

“It is very reassuring to see long-term follow-up data. This is the first time that we have presented the long-term follow-up and I am sure that there is more to come in the coming 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 the clinical implications of findings from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856).

EV-302/KEYNOTE-A39 examined enfortumab vedotin-efjv (Padcev) plus pembrolizumab (Keytruda) for the treatment of treatment-naive patients with locally advanced or metastatic urothelial carcinoma. Updated findings from the study, which were presented during the 2025 Genitourinary Cancers Symposium, demonstrated that the median overall survival among patients who received the combination (n = 442) was 33.8 months (95% CI, 26.1-39.3) compared with 15.9 months (95% CI, 13.6-18.3) in the chemotherapy arm, (n = 444; HR, 0.51; 95% CI, 0.43-0.61; nominal 2-sided P = .00001). The median progression-free survival per blinded independent central review was 12.5 months (95% CI, 10.4-16.6) vs 6.3 months (95% CI, 6.2-6.5), respectively (HR, 0.48; 95% CI, 0.41-0.57; nominal 2-sided P < .00001).

In terms of safety, the frequency and severity of adverse effects in the combination arm was consistent with what was reported in the primary analysis with no new safety signals. The study authors concluded that their findings reinforce enfortumab vedotin plus pembrolizumab as the standard of care in this patient population.

These long-term follow-up data are reassuring and were presented for the first time during the meeting, Gupta began. Additional data with enfortumab vedotin plus pembrolizumab is expected to be presented in the coming years, she added. Notably, findings from the 5-year follow-up of the phase 1/2 EV-103 trial (NCT03288545) showed that efficacy with the combination was being maintained over a long follow-up in patients with cisplatin–ineligible locally advanced or metastatic urothelial carcinoma, she noted.