Dr. Gupta Explores Promising Outcomes for Urothelial Carcinoma Treatment

Dr. Shilpa Gupta, MD, has outlined significant advancements in the treatment of urothelial carcinoma through the use of enfortumab vedotin (Padcev) in combination with pembrolizumab (Keytruda). Speaking at the 2025 Genitourinary Cancers Symposium, she discussed findings from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856), which demonstrated that treatment-naive patients with locally advanced or metastatic urothelial carcinoma benefited substantially in terms of overall survival (OS) when treated with this combination compared to traditional chemotherapy.

The trial results revealed a compelling OS benefit for those receiving enfortumab vedotin plus pembrolizumab. Specifically, the hazard ratio was 0.51 (95% CI, 0.43-0.61; nominal 2-sided P = .00001), indicating that patients had a significantly improved chance of survival. Furthermore, the combination therapy also yielded a noteworthy enhancement in progression-free survival (PFS), with a hazard ratio of 0.48 (95% CI, 0.41-0.57; nominal 2-sided P < .00001).

Key Findings on Patient Subgroups and Safety Profile

The benefits of enfortumab vedotin plus pembrolizumab were consistent across various prespecified patient subgroups. Notably, the most pronounced improvement in OS was observed among patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, achieving a hazard ratio of 0.394 (95% CI, 0.296-0.524). This underscores the potential of this regimen, particularly for patients with better performance status.

Regarding safety, the profile of the combination treatment was in line with previous studies, with no new safety signals reported. Dr. Gupta emphasized that these findings support the use of this regimen as a standard of care for this patient demographic.

Future Research Directions

Looking ahead, researchers plan to delve deeper into the treatment responses and assess potential dose modifications for patients who demonstrate positive outcomes. Dr. Gupta noted that earlier studies suggest the ability to maintain the OS benefit with fewer therapy cycles, indicating the need for further exploration in this area.

The findings from the EV-302/KEYNOTE-A39 trial represent a significant step forward in the management of urothelial carcinoma, providing hope for improved patient outcomes through innovative therapeutic combinations. As research progresses, the focus will remain on optimizing treatment strategies to enhance survival and quality of life for those affected by this challenging disease.