Comparative Cost-Effectiveness Analysis of First-Line Immunotherapy for Advanced Melanoma Based on 10-Year Clinical Outcomes

BACKGROUND: Recently, the CheckMate 067, KEYNOTE-006, and RELATIVITY-047 trials demonstrated the long-term efficacy and safety of 5 first-line therapies for advanced melanoma, including nivolumab + relatlimab, with >10 years of follow-up. However, the long-term economic outcomes are still unclear. This study aimed to assess the comparative cost-effectiveness of these strategies from a US health care perspective using more than a decade of clinical trial data. METHODS: Based on the data from clinical trial reports, we simulated a cohort of 1,662 patients with advanced melanoma across 5 treatment groups in which patients received ipilimumab, nivolumab, pembrolizumab, nivolumab + ipilimumab, or nivolumab + relatlimab as first-line therapy. A flexible parametric survival model was used, combined with background mortality rates, to estimate patients' lifetime overall survival and progression-free survival. A partitioned survival model was constructed to assess the total cost, quality-adjusted life-years (QALYs), total life-years, and incremental cost-effectiveness ratios (ICERs) for the 5 treatment strategies. Sensitivity analyses, including univariate, probabilistic, scenario, and subgroup analyses, were conducted to evaluate the robustness of the model and population differences. RESULTS: Nivolumab + ipilimumab provided the highest QALYs (7.30), followed by nivolumab + relatlimab (6.67 QALYs). Ipilimumab and nivolumab + relatlimab were associated with the lowest ($239,168) and highest ($471,610) costs, respectively. Compared with nivolumab, only nivolumab + ipilimumab resulted in ICERs below the willingness-to-pay threshold of $150,000/QALY. Drug costs and body weight were the most influential factors affecting ICERs. Nivolumab + ipilimumab demonstrated the highest probability of being the most cost-effective strategy. CONCLUSIONS: Among first-line immunotherapy strategies for advanced melanoma, nivolumab + ipilimumab and nivolumab + relatlimab provided the greatest survival benefits. After integrating treatment costs, safety, and health-related quality of life, nivolumab + ipilimumab was the most cost-effective strategy under base-case assumptions, followed by nivolumab monotherapy.