MADRID – For patients with resectable stage III melanoma, adjuvant therapy with the programmed death 1 (PD-1) immune checkpoint inhibitor nivolumab (Opdivo) was associated with significantly longer relapse-free survival compared with the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy), results of a randomized phase 3 trial show.
Among 906 patients who underwent complete resection of stage IIIB, IIIC, or stage IV melanoma in the, the rates of relapse-free survival (RFS), the primary endpoint, were 71% at 12 months for patients assigned to adjuvant nivolumab, compared with 61% for adjuvant ipilimumab. At 18 months, the respective RFS rates were 66% and 53%, reported Jeffrey Weber, MD, PhD, of NYU Langone Health’s Perlmutter Cancer Center in New York City.
However, longer follow-up will be needed to see whether the RFS advantage of nivolumab translates into an overall survival advantage, he acknowledged.
In the trial, patients with high-risk, completely resected stage IIIB, IIIC, or IV melanoma were stratified by disease stage and PD-L1 status at baseline and randomly assigned in cohorts of 453 patients each to receive either nivolumab 3 mg/kg intravenously every 2 weeks and ipilimumab placebo every 3 weeks for four doses, or to ipilimumab 10 mg/kg IV every 3 weeks for four doses, then every 12 weeks from week 24, and nivolumab placebo IV every 2 weeks.
The maximum duration of therapy was 1 year.
For the primary RFS endpoint, the hazard ratio (HR) favoring nivolumab was 0.65 (P less than .0001).
The benefit for nivolumab was observed across the majority of prespecified subgroups tested, including PD-L1 and BRAF mutational status, Dr. Weber said.
Nivolumab also had a better safety profile, with a 14.4% incidence of grade 3 or 4 treatment-related adverse events, compared with 45.9% for ipilimumab. Grade 3 or 4 treatment-related adverse events leading to discontinuation of therapy occurred in 4.6% of patients on nivolumab, compared with 30.9% of those on ipilimumab.
Two patients in the ipilimumab arm died from toxicities related to therapy, one from marrow aplasia, and one from colitis. Both of these deaths occurred more than 100 days after the patients received their last dose of ipilimumab. There were no treatment-related deaths in the nivolumab arm.
Commenting on both the Checkmate 238 trial and a second trial reported at ESMO (COMBI-AD) looking at a combination of dabrafenib and trametinib for patients with stage III melanoma with a BRAF V600 mutation, Olivier Michielin, MD, PhD, said that “we now have, with the data, two fantastic new options. We couldn’t dream those studies to be so positive. This is really something that will open new futures for our patients.”
Dr. Michielin and Dr. Dummer were invited commentators at the briefing. Dr. Michielin was not involved in either trial. Dr. Dummer was a coinvestigator for the COMBI-AD trial.
The study wassimultaneously online by the New England Journal of Medicine.
Checkmate 238 was funded by Bristol-Myers Squibb and Ono Pharmaceutical. Dr. Weber disclosed honoraria, consulting fees, and travel accommodations/expenses from BMS and multiple other companies. Dr. Michielin disclosed consulting and/or honoraria from Amgen, BMS, Roche, MSD, Novartis, and GSK. Dr. Dummer reported advising/consulting roles with BMS and others.