OBJECTIVES: To evaluate the cost-effectiveness of the treatment sequence nivolumab plus ipilimumab (NIVO+IPI) followed by dabrafenib plus trametinib (DAB+TRAM) at progression (NIVO+IPI->DAB+TRAM) versus DAB+TRAM followed by NIVO+IPI at progression (DAB+TRAM->NIVO+IPI) for previously untreated BRAF mutant metastatic melanoma.

METHODS: A 3-state partitioned-survival model was developed using efficacy and safety data from the Phase III DREAMseq trial. DREAMseq has a median follow-up of 22.7 months for overall survival (OS). Due to the lack of individual patient data, OS and progression free survival (PFS) Kaplan-Meier (KM) curves were digitized and extrapolated over a 40-year time horizon using parametric and spline models. First-line treatment duration of NIVO+IPI was informed by the time to discontinuation (TTD) KM from an external trial (CheckMate-067) capping to 84 weeks as in DREAMseq. For DAB+TRAM, the modelled PFS was used as a proxy as no TTD were available. Utility data were sourced from the NICE melanoma guidelines. Costs of drugs, disease management, adverse events, and subsequent treatments were sourced from United Kingdom (UK) official websites (2023 GBP). A discount rate of 3.5% was applied for costs and benefits. Outcomes were quality-adjusted life years (QALYs), total costs, and incremental cost-utility ratios. Sensitivity analyses were conducted to assess the model’s robustness. The analysis was conducted from a UK healthcare payer perspective.

RESULTS: NIVO+IPI->DAB+TRAM dominated DAB+TRAM->NIVO+IPI with higher QALYs (7.60 vs 4.41) and less costs (£255,669 vs £372,939), resulting in a QALY gain of 3.19 and a cost saving of £117,269. Probabilistic sensitivity analysis results were stable with 1,000 iterations. NIVO+IPI->DAB+TRAM remained dominant in all scenario analyses, indicating model results were robust to alternative assumptions.

CONCLUSIONS: In conclusion, our study presents compelling modeling evidence demonstrating that dual immunotherapy with NIVO+IPI followed by BRAF+MEK inhibitors, at progression, is a more cost-effective treatment sequence for the management of patients with BRAF mutant metastatic melanoma.