The objective of this study is to evaluate the cost-effectiveness of nivolumab+ipilimumab (NIVO+IPI) versus existing treatments in first-line treatment of patients with advanced melanoma from a US payer perspective using recently reported 28-month survival data from the CheckMate 067 phase III trial.
This three-state partitioned survival model was developed from projections of overall survival (OS) and progression-free survival (PFS) based on a network meta-analysis that considers time-varying hazard ratios to estimate accrued quality adjusted survival, total drug acquisition, follow-up, and toxicity costs over a lifetime time horizon (30 years). Competing treatments included NIVO, IPI, pembrolizumab (PEM), dabrafenib+trametinib (DAB+TRA), DAB, vemurafenib+cobimetinib (VEM+COB), VEM, and dacarbazine (DTIC). Costs and adverse event frequencies were obtained from expert input, publically available sources, and literature. Utility weights were estimated from the CheckMate 067 trial. Incremental analysis is summarized as incremental cost-utility ratios (ICURs) for NIVO+IPI. A 3.5% discount rate is applied to costs ($US 2016) and utilities.
NIVO+IPI is projected to have the greatest accrued survival among the competing treatments with 6.015 LY and 4.979 QALY and also the highest costs ($291,096 including treatment acquisition, follow-up, management of adverse events, and post-progression costs) over the 30-year time horizon. Pairwise ICURs for NIVO+IPI vs. other treatments ranged from $34,774 per QALY (vs. DAB+TRA) to $92,647 per QALY (vs. NIVO). In extended dominance analysis, DTIC, NIVO, and NIVO+IPI form the cost-effectiveness frontier, showing that these are the most cost-effective options at different willingness to pay thresholds. Probabilistic sensitivity analysis generated results consistent with the base case for NIVO+IPI.
The large survival gains of NIVO+IPI make it a cost-effective option for first-line treatment of advanced melanoma when compared to other immune-oncologic therapies, targeted agents, and chemotherapy.
Clinical trial identification
Cost study based on the 067 trial NCT01844505 protocol number is CA209-067 (CheckMate 067)
Legal entity responsible for the study
J. Sabater, K. Gupte-Singh, S. Kotapati, S. Rao: Employed by Bristol-Myers Squibb and owns stock in Bristol-Myers Squibb. T. Baker: ICON is contracted to undertake the nivolumab analysis for Bristol-Myers Squibb and ICON pays me as a consultant to the project. V. Paly: Outside of support received from Bristol-Myers Squibb in preparation of the core model and market specific adaptations. A. Briggs: ICON is contracted to undertake the nivolumab analysis for Bristol-Myers Squibb and ICON pays me as a consultant to the project. All other authors have declared no conflicts of interest.