Gupta Highlights Promising Outcomes of Enfortumab Vedotin and Pembrolizumab

Dr. Shilpa Gupta, the director of Genitourinary Medical Oncology at the Taussig Cancer Institute and coleader of the Genitourinary Oncology Program at the Cleveland Clinic, recently outlined future research directions for the combination therapy of enfortumab vedotin (Padcev) and pembrolizumab (Keytruda) in treating urothelial carcinoma. This discussion took place during the 2025 Genitourinary Cancers Symposium, where significant findings were presented from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856).

The trial results indicated that treatment-naive patients suffering from locally advanced or metastatic urothelial carcinoma who received the combination therapy experienced a notable overall survival (OS) benefit compared to those who received standard chemotherapy. Specifically, the study reported a hazard ratio (HR) of 0.51 (95% confidence interval [CI], 0.43-0.61; nominal 2-sided P = .00001) for OS. Additionally, patients on the combination therapy showed a significant improvement in progression-free survival (PFS) with an HR of 0.48 (95% CI, 0.41-0.57; nominal 2-sided P < .00001) when compared to chemotherapy alone.

Key Findings and Implications for Treatment

The OS benefit from enfortumab vedotin combined with pembrolizumab was consistent across several pre-specified patient subgroups. Notably, the most substantial advantage was observed in patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, yielding an HR of 0.394 (95% CI, 0.296-0.524).

Dr. Gupta emphasized that the safety profile associated with this combination regimen was in line with previous findings, revealing no unexpected safety signals. This consistency reinforces the treatment’s potential as a standard of care option for this specific patient population.

Moving forward, researchers plan to investigate the outcomes of patients who achieved responses to the treatment, as well as assess any necessary dose modifications. Dr. Gupta noted that earlier results suggested the possibility of maintaining the overall survival benefit with fewer treatment cycles, which could have significant implications for patient care.

The promising data presented at the symposium highlights a potential shift in the treatment paradigm for urothelial carcinoma, offering hope for improved outcomes among patients. As ongoing research continues to explore the nuances of this combination therapy, the medical community remains optimistic about its role in enhancing patient survival and quality of life.