Adjuvant nivolumab failed to demonstrate a statistically significant improvement in disease-free survival (DFS) compared to placebo in patients with localized renal cell carcinoma (RCC) at high risk of recurrence following nephrectomy. These findings come from Part B of the phase III CheckMate 914 trial, consistent with Part A results that showed no DFS benefit with nivolumab plus ipilimumab versus placebo in the same setting. The study, involving 825 patients across 24 countries, highlights the ongoing challenges in improving outcomes for RCC patients post-surgery.
Study Design and Key Findings
Between March 2020 and March 2022, patients were randomized to receive nivolumab (240 mg every 2 weeks), placebo, or nivolumab plus ipilimumab. The primary endpoint was disease-free survival as assessed by blinded independent central review. After a median follow-up of 27 months, the median DFS was not reached in either the nivolumab or placebo groups. The 18-month DFS rate was 78.4% in the nivolumab arm and 75.0% in the placebo arm (HR = 0.87, 95% CI = 0.62–1.21, P = .40). The combination arm's outcomes were not statistically tested due to the lack of benefit observed in Part A.
Safety Profile
The safety analysis revealed that Grade 3 to 4 adverse events occurred in 17.2% of patients receiving nivolumab, 15.0% receiving placebo, and 28.9% receiving nivolumab/ipilimumab. Treatment-related adverse events led to treatment discontinuation in 9.6%, 1.0%, and 28.4% of patients, respectively, indicating a higher toxicity burden with the combination therapy.
Expert Commentary
According to Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, the corresponding author of the Journal of Clinical Oncology article, "Part B of CheckMate 914 did not meet the primary endpoint of improved disease-free survival for nivolumab vs placebo in patients with localized [renal cell carcinoma] at high risk of postnephrectomy recurrence."
The trial was supported by Bristol Myers Squibb and Ono Pharmaceutical Company Ltd.
