OBJECTIVES

: Nivolumab (NIV) and ipilimumab (IPI) are both new and expensive agents used in first-line immunotherapies for patients with unresectable/metastatic (stage III-IV) advanced melanoma (AM). The study aimed to assess if combination therapy (NIV+IPI) is more cost-effective compared to monotherapy (NIV) for untreated AM patients in the Netherlands.

METHODS

: A Markov model was constructed with a life-time horizon from Dutch healthcare perspective. Future effects and costs were discounted at 1.5% and 4%, respectively. Risks of progression and death were based on progression-free survivals (PFSs) obtained from a phase III clinical trial (NIV+IPI and NIV versus IPI) and conjectural overall survivals (OSs) calculated indirectly by using PFSs and OSs from another one (NIV versus dacarbazine), which were extrapolated by Weibull distribution lateron. Utility values of health states and disutility values of adverse events were derived from literature. Unit costs were taken from Dutch Diagnosis Treatment Combination Care Products Tariff, Erasmus MC prices and Dutch pharmacy purchase prices. Chronic management costs of AM and treatment costs of adverse events were calculated based on a survey done among clinicians determining necessary healthcare services and their utilization rates.

RESULTS

: Over life-time, on average an AM patient being treated by NIV+IPI was estimated to live 4.22 years and 2.59 QALYs at a (discounted) net cost of 262,824.61 EUR, while another being treated by NIV was estimated to live 3.26 years and 2.00 QALYs at a (discounted) net cost of 195,341.79 EUR, per individual. So, the incremental cost-effectiveness ratio was 70,770.30 EUR per life year saved and the incremental cost-utility ratio was 115,533.29 EUR per QALY gained.

CONCLUSIONS

: At a willingness to pay threshold of 80,000.00 EUR per QALY gained, NIV+IPI compared to NIV may not be accepted as a cost-effective tool, from Dutch healthcare perspective, in order to prevent high mortality and morbidity rates of AM.