Nivolumab continues to demonstrate durable protection against melanoma recurrence nearly a decade after treatment, according to new results from the CheckMate 238 trial. The long-term analysis provides the most comprehensive evidence yet of sustained efficacy and safety of the PD-1 inhibitor compared with ipilimumab in patients with resected stage IIIB–C or stage IV melanoma.
Sustained Survival Advantage
The multicentre, randomized trial included patients who had undergone surgery to remove advanced melanoma but were at high risk of recurrence. Participants were assigned to receive either nivolumab (3 mg/kg every 2 weeks) or ipilimumab (10 mg/kg every 3 weeks for four doses, then every 12 weeks) for up to 1 year, or until disease recurrence or unacceptable toxicity.
After a median follow-up period of 107 months, nivolumab demonstrated a clear and lasting benefit. The median recurrence-free survival was 61.1 months with nivolumab versus 24.2 months with ipilimumab, corresponding to a hazard ratio (HR) for recurrence or death of 0.76 (95% CI, 0.63–0.90). At nine years, 44% of patients in the nivolumab group remained recurrence-free, compared with 37% in the ipilimumab group.
Durable Metastasis-Free and Overall Survival
For patients with stage III melanoma, nivolumab also showed a numerical advantage in distant metastasis–free survival, exceeding 9 years compared with 83.8 months for ipilimumab. The nine-year metastasis-free survival rate reached 54% versus 48%, respectively (HR for distant metastasis or death, 0.81; 95% CI, 0.65–1.00). Overall survival remained high in both groups, with 69% of nivolumab patients alive at nine years compared with 65% in the ipilimumab arm (HR for death, 0.88; 95.03% CI, 0.69–1.11).
Clinical Implications
No new late-onset adverse events were reported, and fewer patients required subsequent systemic therapies in the nivolumab group (37.3%) compared with ipilimumab (44.6%). Investigators concluded that the final nine-year data confirm the long-term recurrence-free and metastasis-free benefit of nivolumab in the adjuvant melanoma setting.
Reference
Ascierto PA et al. Nivolumab for resected stage III or IV melanoma at 9 Years. The New England Journal of Medicine. 2025; DOI: 10.1056/NEJMoa2504966.
