OBJECTIVES: To evaluate the cost-effectiveness of fixed-dose combination NIVO+RELA versus SOC for unresectable or metastatic melanoma (including immunotherapies [IOs]: NIVO, pembrolizumab [PEMBRO], nivolumab+ipilimumab [NIVO+IPI], IPI, and BRAF/MEK inhibitors: vemurafenib+cobimetinib [VEM+COBI], dabrafenib+trametinib [DAB+TRAM] and encorafenib+binimetinib [ENCO+BINI]) from a healthcare payer perspective in Canada.

METHODS: A three-state partitioned-survival model was developed. Parametric and piecewise models were fitted to the overall survival (OS) and progression-free survival (PFS) data from the NIVO+RELA and NIVO arms of the all-comers in RELATIVITY-047. To incorporate other comparators, time-varying hazard ratios based on a fractional polynomial network meta-analysis were applied to the modelled PFS and OS NIVO curves from RELATIVITY-047. Costs of drugs, disease management, adverse events, and subsequent treatments were sourced from Canadian official websites (year 2023). Health-state specific utilities were derived from the EQ-5D data collected in RELATIVITY-047 using the Canadian values. A discount rate of 1.5% was applied for costs and outcomes. Model outcomes were average quality-adjusted life years (QALYs), costs, and sequential incremental cost-utility ratios (ICURs) over 25 years. The base case was probabilistic with 4,000 Monte Carlo iterations. Scenario analyses tested robustness of results to modelling assumptions.

RESULTS: NIVO+RELA generated higher QALYs compared to other IOs; total QALYs were 5.74, 4.93, 3.40, 6.38, and 6.89 for NIVO, PEMBRO, IPI, NIVO+IPI, and NIVO+RELA, respectively. Total costs were $235,576, $268,007, $268,964, $274,002, and $371,036, respectively. In the sequential comparison, PEMBRO and IPI were dominated by NIVO, the ICURs were $60,894/QALY for NIVO+IPI versus NIVO and $187,138/QALY for NIVO+RELA versus NIVO+IPI. NIVO+RELA dominated all BRAF/MEK inhibitors, generating higher incremental QALYs (2.86-3.74) with cost savings ($340,334-$718,183). The results were consistent across a range of scenario analyses.

CONCLUSIONS: NIVO+RELA is expected to be a life-extending and cost-effective new therapy compared to SOC treatments for unresectable or metastatic melanoma in Canada.