Extended follow-up from the CheckMate 238 trial confirmed the superior efficacy of nivolumab compared with ipilimumab in patients with stage III and IV resected melanoma.
“There is a clear clinical need for the adjuvant treatment of patients with high-risk stages III and IV resected melanoma,” said Jeffrey S. Weber, MD, PhD, of New York University’s Perlmutter Cancer Center. The 5-year recurrence rates range from 50% to 80% in higher-risk patients, and most recurrences happen within 3 years for stage III patients.
Weber presented results (abstract 9502) of a 24-month follow-up analysis from the CheckMate 238 trial at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago. The trial included 906 patients randomized evenly to receive either nivolumab or ipilimumab, along with matching placebo. Patients had a median age of 56 years in the nivolumab group and 54 years in the ipilimumab group, and 81% in each group had stage III disease. Programmed death ligand 1 (PD-L1) expression of at least 5% was present in 34% of both groups.
The median recurrence-free survival was 30.8 months with nivolumab and 24.1 months with ipilimumab, for a hazard ratio (HR) of 0.66 (95% CI, 0.54–0.81; P < .0001). This benefit was seen across a number of prespecified subgroup analyses, including both PD-L1 expression above and below 5%, stage III and IV disease, and regardless of BRAF mutation status.
There was also benefit with regard to distant metastasis–free survival (DMFS), which was considered an exploratory endpoint. The median was not reached in either group, but there were more DMFS events in the ipilimumab group (126 events out of 366 patients at risk) than in the nivolumab group (107 events out of 370 patients at risk), for an HR of 0.76 (95% CI, 0.59–0.98; P = .0340).
“With extended follow-up nivolumab demonstrated a sustained efficacy benefit vs the active comparator of ipilimumab,” Weber said. “These more mature data continue to demonstrate durable clinical benefit with nivolumab and further support its use for patients with resected stage III or IV melanoma.”
April K. S. Salama, MD, of the Duke Cancer Institute in Durham, North Carolina, was the discussant for the session, and she also highlighted the benefit seen across nearly every subgroup in the trial. As has been reported previously, she noted, “the rate of severe immune-related adverse events with nivolumab is markedly reduced compared to ipilimumab. …This makes anti–PD-1 therapy the preferred immunotherapy regimen for these patients.”