Dr Galsky on the Efficacy of Adjuvant Nivolumab in the CheckMate 274 Trial in mUC

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 how updated findings from the phase 3 CheckMate 274 trial (NCT02632409) confirm the efficacy of adjuvant systemic immunotherapy in metastatic urothelial carcinoma.

CheckMate 274 was a randomized, phase 3 study of adjuvant nivolumab (Opdivo) vs placebo in patients with muscle-invasive urothelial cancer at a high risk for recurrence after surgery, Galsky begins. High recurrence risk was defined as either pathological T2 or above disease in patients who had neoadjuvant cisplatin-based chemotherapy, or pathological T3 and higher disease in patients who did not receive neoadjuvant cisplatin-based chemotherapy and were not eligible or refused adjuvant cisplatin-based chemotherapy, Galsky details. The study's co-primary end points were disease-free survival (DFS) in both the all-comer population and in patients with positive PD-L1 expression.

Extended follow-up data from CheckMate 274 were presented at the 2023 Genitourinary Cancers Symposium, Galsky reports. At a median follow-up of 36.1 months, adjuvant nivolumab produced a median DFS of 22.0 months (95% CI, 18.8-36.9) vs 10.9 months (95% CI, 8.3-15.2) with placebo (HR, 0.71; 95% CI, 0.58-0.86) in the intent-to-treat population. In the PD-L1–positive subgroup, the median DFS was 52.6 months (95% CI, 25.8-not estimable) for nivolumab vs 8.4 months (95% CI, 5.6-17.9) for placebo (HR, 0.52; 95% CI, 0.37-0.72).

The effect size for DFS in both populations was consistent with initial results from the study, which had been previously published in the New England Journal of Medicine, Galsky continues. The trial demonstrated superior median DFS with nivolumab vs placebo at a minimum follow-up of 5.9 months. At this time, median DFS had not yet been reached with nivolumab in patients with a PD-L1 expression of 1% or higher.

Based on these data, adjuvant nivolumab was granted regular approvalby the FDA for the treatment of this patient population in August 2021, Galsky says.

Several other secondary or exploratory end points from the updated analysis showed similar effect size compared with the initial readout, including non–urothelial tract recurrence-free survival, and distant-metastasis free survival, Galsky adds. Notably, the required number of overall survival (OS) events has not yet been met to formally perform an OS analysis.

The sustained benefit seen with nivolumab even after the completion of therapy is encouraging, as this treatment is administered for a fixed duration of 1 year in the adjuvant setting, Galsky concludes.