First-line pembrolizumab followed by second-line ipilimumab or first-line nivolumab followed by second-line ipilimumab are the most cost-effective, immunotherapeutic options for patients with treatment-naïve BRAF wild-type advanced melanoma, according to a study published in the Journal of Clinical Oncology.1 

Only approximately 17% of patients with stage IV metastatic melanoma are expected to live 5 years beyond diagnosis. Although randomized controlled trials have demonstrated improved patient outcomes with new immune checkpoint inhibitors like pembrolizumab, nivolumab, and ipilimumab, the optimal treatment sequence in patients with BRAF wild-type advanced melanoma remains unclear.

To inform policy makers about the value of these novel agents, researchers sought to conduct a cost-effectiveness analysis of different sequencing of these agents for metastatic melanoma.

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The investigators used Markov models with a US-payer perspective and lifetime horizon to estimate 2016 costs and quality-adjusted life years (QALYs) for treatment sequences with frontline nivolumab, ipilimumab, nivolumab plus ipilimumab, pembrolizumab every 2 weeks, and pembrolizumab every 3 weeks. They obtained data on rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from phase 3 trials.

Results showed that pembrolizumab every 3 weeks followed by ipilimumab as second-line therapy was both more effective and less costly than treatment sequences that involved first-line dacarbazine, ipilimumab, and pembrolizumab every 2 weeks.

Investigators found that nivolumab followed by ipilimumab produced an incremental cost-effectiveness ratio (ICER) of $90,871/QALY compared with first-line dacarbazine. In addition, first-line nivolumab plus ipilimumab followed by platinum and taxane chemotherapy was associated with an ICER of $198,867/QALY vs the frontline dacarbazine strategy.

Nivolumab plus ipilimumab followed by second-line chemotherapy was not cost-effective on the basis of a willingness-to-pay threshold of $100,000/QALY.

These findings support the use of a PD-1 inhibitor as first-line monotherapy followed by second-line ipilimumab as the most cost-effective approach in this population.


1. Kohn CG, Zeichner SB, Chen Q, Montero AJ, Goldstein DA, Flowers CR. Cost-effectiveness of immune checkpoint inhibition in BRAF wild-type advanced melanoma. J Clin Oncol. 2017 Feb 21. doi: 10.1200/JCO.2016.69.6336 [Epub ahead of print]