Results from the phase 3 Checkmate 914 trial demonstrate that adjuvant treatment with nivolumab/ipilimumab does not improve survival in patients with stage II-III localized renal cell carcinoma (RCC) who have a substantial risk for post-nephrectomy relapse.
Patients with stage II-III localized renal cell carcinoma (RCC) have a substantial risk for post-nephrectomy relapse. Approved adjuvant therapeutic options include sunitinib and pembrolizumab. Dual immune checkpoint blockade with nivolumab and ipilimumab has demonstrated long-term improvements versus sunitinib in patients with untreated advanced RCC. Based on these findings, the phase 3 Checkmate 914 trial evaluated the clinical outcomes of adjuvant nivolumab/ipilimumab in the setting of surgically resected stage II-III clear-cell RCC with a high risk for recurrence. Dr. Robert Motzer (Memorial Sloan Kettering Cancer Center) presented the results at ESMO 2022.
A total of 816 patients were randomized 1:1 to receive nivolumab (240 mg every 2 weeks, 12 doses) plus ipilimumab (1 mg/kg every 6 weeks, 4 doses) or placebo after radical or partial nephrectomy with negative surgical margins. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival (OS) and safety. If the DFS endpoint was not significant, no formal analysis of OS would be performed.
With 37.0 months of median follow-up, the primary endpoint of DFS was not met (HR, 0.92; P=0.53). DFS rates at 24 months were 76.4% in the nivolumab/ipilimumab arm and 74.0% in the placebo arm. Of note, discontinuation of treatment rates were 43% in the nivolumab/ipilimumab arm and 11% in the placebo arm. Incidence rates of treatment-related adverse events grade 3 or higher were 28% and 2%, respectively.
Based on these results, Dr. Motzer concluded that “adjuvant treatment with nivolumab/ipilimumab does not improve survival in patients with stage II-III localized RCC, who have a substantial risk for post-nephrectomy relapse. The safety of nivolumab/ipilimumab in this population is consistent with the known profile of this combination in patients with advanced RCC.”
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