Dr Gopal on the Significance of the EV-302 and CheckMate 901 Trials in mUC

Nikhil A. Gopal, MD, assistant professor, urology, assistant professor, College of Medicine - Memphis, Department of Urology, The University of Tennessee Health Science Center, discusses how the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) and CheckMate 901 trials (NCT03036098) have shifted the treatment paradigm in metastatic urothelial cancer.

These 2 studies, which were presented at the 2023 ESMO Congress, showed a survival benefit beyond platinum-based chemotherapy alone, further reshaping the treatment paradigm for metastatic urothelial carcinoma, Gopal begins.

The first of these was the CheckMate 901 trial evaluating the triplet regimen of nivolumab (Opdivo) plus gemcitabine and cisplatin in metastatic or unresectable urothelial carcinoma, Gopal states. The triplet showed a survival benefit in the frontline setting for cisplatin-eligible patients, producing a median OS of 21.7 months (95% CI, 18.6-26.4) vs 18.9 months (95% CI, 14.7-22.4) with chemotherapy alone (HR, 0.78; 95% CI, 0.63-0.96; P = .0171), he details. Although the trial represents one of the first studies to demonstrate a prolonged survival benefit with cisplatin-based chemotherapy and immunotherapy in the frontline setting, these results were accompanied b by equally impressive findings from the EV-302 study, Gopal notes.

EV-302 investigated enfortumab-ejfv (Padcev) vedotin plus pembrolizumab (Keytruda) vs standard-of-care (SOC) platinum-based chemotherapy therapy in treatment-naive patients with metastatic urothelial cancer. The regimen produced a median OS of 31.5 months (95% CI, 25.4-not reached) vs 16.1 months (95% CI, 13.9-18.3) with chemotherapy at a median follow-up of 17.2 months, Gopal reports.

Consequently, enfortumab vedotin plus pembrolizumab has become the SOC in the frontline setting for metastatic urothelial carcinoma following its full FDA approval for patients with locally advanced or metastatic urothelial cancer on December 15, 2023, Gopal says. This combination therapy has demonstrated superiority over traditional agents used in this setting, which were primarily platinum-based chemotherapy combinations, Gopal states. Prior to the approval of this regimen, patients had not consistently experienced a sustained overall survival (OS) benefit from standard therapies beyond approximately 18 to 20 months, Gopal explains.

Despite its efficicy, the accessibility and cost of this treatment remain important real-world considerations, especially given its higher cost compared to platinum-based therapy, Gopal notes. Nonetheless, the approval of enfortumab vedotin plus pembrolizumab represents a paradigm shift in the management of metastatic urothelial carcinoma, particularly for cisplatin-ineligible patients who previously lacked effective treatment options, he concludes.