As reported in the Journal of Clinical Oncology by Jeffrey S. Weber, MD, PhD, and colleagues, the phase III CheckMate 915 trial showed no improvement in recurrence-free survival with adjuvant nivolumab/ipilimumab vs nivolumab in patients with resected stage IIIB–D or IV melanoma.

Jeffrey S. Weber, MD, PhD

Study Details

In the double-blind trial, 1,833 patients from sites in 19 countries were randomly assigned between April 2017 and June 2018 to receive nivolumab at 240 mg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks (n = 916) or placebo plus nivolumab at 480 mg every 4 weeks (n = 917) for up to 1 year. The dual primary endpoints were recurrence-free survival among all randomly assigned patients and in the tumor PD-L1 expression level < 1% subgroup; the latter consisted of 349 patients in the combination group and 351 in the nivolumab group.

Recurrence-Free Survival

At a minimum follow-up of approximately 23.7 months (median = 28.0 months in combination group and 28.1 months in nivolumab group), median recurrence-free survival was not reached in either group among all randomly assigned patients. Rates at 24 months were 64.6% in the combination group vs 63.2% in the nivolumab group (hazard ratio [HR] = 0.92, 97.3% confidence interval [CI] = 0.77–1.09, P = .269).  

Among patients in the PD-L1 < 1% subgroup, median recurrence-free survival was 33.2 months (95% CI = 22.2 months–not reached) in the combination group vs 25.3 months (95% CI = 19.8 months–not reached) in the nivolumab group (HR = 0.91, 95% CI = 0.73–1.14, P = .417). Rates at 24 months were 53.6% vs 52.4%.  

Median distant metastasis–free survival was not reached in either the combination or nivolumab groups among all patients (24-month rates = 75.4% vs 77.4%; HR = 1.01, 95% CI = 0.83–1.23) or in the PD-L1 < 1% subgroup (24-month rates = 67.9% vs 68.4%; HR = 0.94, 95% CI = 0.70–1.25). Median overall survival was not reached in either the combination group or the nivolumab group among all patients (24-month rates = 89.8% vs 91.8%; HR = 1.09, 95% CI = 0.80–1.32) or in the PD-L1 < 1% subgroup (24-month rates = 85.3% vs 89.6%; HR = 1.22, 95% CI = 0.85–1.73).

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 32.6% of patients in the combination group vs 12.8% of the nivolumab group. The most common were increased lipase (5.2%) and increased alanine aminotransferase (3.3%) in the combination group and increased lipase (1.9%) in the nivolumab group. Any-grade treatment-related adverse events led to discontinuation of treatment in 31.6% of patients in the combination group (grade 3 or 4 in 18.9%) vs 10.4% of the nivolumab group (grade 3 or 4 in 5.9%). Treatment-related death occurred in four patients (0.4%) in the combination group, due to respiratory distress syndrome, myasthenia gravis, pneumonitis, and liver failure, respectively. No treatment-related deaths occurred in the nivolumab group.

The investigators concluded, “Nivolumab [at] 240 mg once every 2 weeks plus ipilimumab [at] 1 mg/kg once every 6 weeks did not improve recurrence-free survival vs nivolumab [at] 480 mg once every 4 weeks in patients with stage IIIB–D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.”

Dr. Weber, of the Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.