Patients with stage II–III localised RCC have a substantial risk for post-nephrectomy relapse1. Approved adjuvant therapeutic options include sunitinib (USA only) and pembrolizumab2. Dual immune checkpoint blockade with nivolumab and ipilimumab has demonstrated long-term improvements versus sunitinib in patients with untreated advanced RCC3.
Therefore, the phase 3 Checkmate 914 (NCT03138512) 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 of recurrence. Dr Robert Motzer (Memorial Sloan Kettering Cancer Center, NY, USA) presented the results4.
A total of 816 patients were randomised 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 of 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 versus 74.0% in the placebo arm. Of note, discontinuation of treatment was 43% in the nivolumab/ipilimumab arm versus 11% in the placebo arm. Incidence of treatment-related adverse events grade 3 or more was 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 localised 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.”