As reported at the latest ESMO Congress and in The New England Journal of Medicine by Ascierto et al, the 9-year follow-up of the phase III CheckMate 238 trial showed a continued recurrence-free survival benefit with adjuvant nivolumab vs ipilimumab in patients with resected stage IIIB–C or IV melanoma. The primary analysis of the trial showed superior recurrence-free survival with nivolumab.
Study Details
In the international double-blind trial, 906 patients were randomly assigned between March and November 2015 to receive nivolumab at 3 mg/kg every 2 weeks (n = 453) or ipilimumab at 10 mg/kg every 3 weeks (n = 453) for four doses and every 12 weeks thereafter, both for up to 1 year or until disease progression or unacceptable toxicity. The primary endpoint was recurrence-free survival; secondary endpoints included distant metastasis–free survival and overall survival.
Key Findings
At a minimum follow-up of 9 years, median recurrence-free survival was 61.1 months (95% confidence interval [CI] = 42.9–89.2 months) in the nivolumab group vs 24.2 months (95% CI = 16.6–35.1 months) in the ipilimumab group (hazard ratio [HR] = 0.76, 95% CI = 0.63–0.90); the 9-year rate was 44% vs 37%.
The median duration of distant metastasis–free survival in patients with stage III disease was not reached (95% CI = 77.1 months to not reached) in the nivolumab group vs 83.8 months (95% CI = 44.9 months to not reached) in the ipilimumab group (HR = 0.81, 95% CI = 0.65–1.00); the 9-year rate was 54% vs 48%.
The median overall survival was not reached (95% CI = not reached to not reached) in the nivolumab group vs not reached (95% CI = not reached to not reached) in the ipilimumab group, with 128 deaths observed in the nivolumab group vs 142 deaths in the ipilimumab group (HR = 0.88, 95.03% CI = 0.69–1.11); the 9-year rate was 69% vs 65%. Rates of melanoma-specific death at 9 years were 26% in the nivolumab group vs 30% in the ipilimumab group (HR = 0.87, 95% CI = 0.67–1.13).
Subsequent systemic therapy was received by 37.3% of the nivolumab group vs 44.6% of the ipilimumab group. No new late adverse events were observed over extended follow-up.
The investigators concluded: “The 9-year final data support a sustained finding of longer recurrence-free survival with nivolumab than with ipilimumab.”
Paolo A. Ascierto, MD, of the Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori, Naples, Italy, is the corresponding author of The New England Journal of Medicine article.
Disclosure: The study was funded by Bristol Myers Squibb and Ono Pharmaceutical. For full disclosures of all study authors, visit nejm.org.
