Cost-effectiveness of nivolumab-ipilimumab combination therapy compared with monotherapy for first-line treatment of metastatic melanoma in the United States

Abstract

BACKGROUND: The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. OBJECTIVE: To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as first- line therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients. METHODS: A 3-state Markov model (PD-L1 positive stable disease, PD-L1 negative stable disease, and progression and/or death) was developed using a U.S. societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free (PF) survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 U.S. dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilim- umab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. RESULTS: Nivolumab-ipilimumab combination therapy was not the cost-effective choice ($454,092 per PF quality-adjusted life-year [[]QALY]) compared with nivolumab monotherapy in a base case analysis at a willingness-to-pay threshold of $100,000 per PFQALY. Combination therapy and nivolumab monotherapy were cost-effective choices compared with ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncer- tainty to the model. In a population of 100[%] PD-L1 negative patients, nivolumab was still the optimal treatment, but combination therapy had an improved incremental cost-effectiveness ratio (ICER) of $295,903 per PFQALY. Combination therapy became dominated by nivolumab, when 68[%] of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to < $21,555 per dose for combination therapy to have an ICER < $100,000 per PFQALY and to < $19,151 (a 42[%] reduction) to be more cost-effective than nivolumab monotherapy. CONCLUSIONS: Nivolumab-ipilimumab combination therapy was not cost- effective compared with nivolumab monotherapy, which was the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions, and future cost-effectiveness studies are completed. ANNA OH, MSN, MPH, RN, Department of Social and Behavioral Sciences, School of Nursing, University of California, San Francisco. DANG M. TRAN, BS; LEANN C. MCDOWELL, PharmD; DOR KEYVANI, PharmD; JAY ANDREW BARCELON, BS; OSCAR MERINO, BS; and LESLIE WILSON, PhD, Department of Clinical Pharmacy, University of California, San Francisco.