In an analysis reported in the Journal of Clinical Oncology, Georgina V. Long, PhD, MBBS, and colleagues performed an indirect comparison of outcomes with first-line nivolumab/relatlimab vs nivolumab/ipilimumab for advanced melanoma using patient-level data from trials supporting approval of the two regimens: RELATIVITY-047 and CheckMate 067, respectively. No direct comparisons of the regimens in this setting have been reported previously.
Georgina V. Long, PhD, MBBS
Study Details
In the comparison, inverse probability of treatment weighting (IPTW) was used to adjust for baseline characteristic differences between patients in the two studies. Minimum follow-up was 33 months in RELATIVITY-047 and 36 months in CheckMate 067.
Key Findings
After IPTW, baseline characteristics were balanced for 339 patients receiving nivolumab/relatlimab and 297 receiving nivolumab/ipilimumab. On investigator assessment, for nivolumab/relatlimab vs nivolumab/ipilimumab, 36-month progression-free survival was 36% vs 39% (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.88–1.33), objective response rates were 48% vs 50% (odds ratio = 0.91, 95% CI = 0.73–1.14), and 36-month melanoma-specific survival was 65% vs 62% (HR = 0.86, 95% CI = 0.67–1.12). Overall survival at 36 months was 57% vs 57% (HR = 0.94, 95% CI = 0.75–1.19).
Outcomes in the two groups were similar in most subgroups examined. Although the analysis was limited by small numbers of patients, larger numeric benefits with nivolumab/ipilimumab were observed in progression-free survival among patients with acral melanoma (HR = 1.42, 95% CI = 0.69–2.93), and in overall survival among patients with acral melanoma (HR = 1.72, 95% CI = 0.76–3.91) as well as those with a lactate dehydrogenase level > 2 × upper limit of normal (HR = 1.50, 95% CI = 0.85–2.66).
Nivolumab/relatlimab was associated with fewer grade 3 or 4 treatment-related adverse events (23% vs 61%) and any-grade treatment-related adverse events leading to discontinuation of treatment (17% vs 41%) than nivolumab/ipilimumab.
The investigators concluded, “Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most—but not all—subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.”
Dr. Long, of the Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, 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.
