Dr. Galsky on the Rationale for the CheckMate-274 Trial in Urothelial Cancer

Matthew Galsky, MD, professor of medicine, hematology and medical oncology, professor of urology, director of Genitourinary Medical Oncology, codirector, the Center of Excellence for Bladder Cancer, and associate director, Translational Research at the Tisch Cancer Institute, Mount Sinai, discusses the rationale of the phase 3 CheckMate-274 trial (NCT02632409) in patients with urothelial cancer.

CheckMate-274 trial evaluated adjuvant nivolumab (Opdivo) vs placebo in patients with muscle-invasive urothelial cancer at high risk for recurrence after radical surgery. Prior findings from the study led to the FDA approval of nivolumab for the adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection in August 2021. Updated data presented at the 2023 Genitourinary Cancers Symposium reaffirmed the benefit of nivolumab in this setting after long-term follow-up.

When enrolling patients for the study, high risk of recurrence was defined by pathological stage. The trial included patients who had neoadjuvant chemotherapy and had pathological T2 or higher urothelial cancer in their surgical specimen and those who didn't have neoadjuvant chemotherapy and had pathological T3 or higher disease in their surgical specimen, but were cisplatin ineligible, Galsky says.

Prior to conducting the study, data were not available to help guide treatment in this setting to mitigate the risk of recurrence for these patients, and CheckMate-274 aimed to address that unmet need, Galsky continues.

The previously reported data that led to nivolumab’s approval in this indication were presented with a minimum follow up of 5.9 months. The co-primary end points of the trial included disease-free survival (DFS) in the intent-to-treat population and DFS in patients with tumors with PD-L1 expression of at least 1%. The primary analysis showed nivolumab led to an improvement in DFS in both of those populations compared with placebo, meeting the co-primary end points, Galsky concludes.