The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England

Abstract

Background Nivolumab was the first programmed death receptor 1 (PD-1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients. Objective To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Methods A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab, dabrafenib, and vemurafenib for BRAF mutation-positive patients. Covariate-adjusted parametric curves for time to progression, pre-progression survival, and post-progression survival were fitted based on patient-level data from two trials and long-term ipilimumab survival data. Indirect treatment comparisons between nivolumab, ipilimumab, and dacarbazine were informed by these covariate-adjusted parametric curves, controlling for differences in patient characteristics. Kaplan-Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib. Patient utilities and resource use data were based on trial data or the literature. Patients are assumed to receive nivolumab until there is no further clinical benefit, assumed to be the first of progressive disease, unacceptable toxicity, or 2 years of treatment. Results Nivolumab is the most cost-effective treatment option in BRAF mutation-negative and mutation-positive patients, with incremental cost-effectiveness ratios of £24,483 and £17,362 per quality-adjusted life year, respectively. The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves. Conclusions Nivolumab is a cost-effective treatment for advanced melanoma patients in England.

Economic Evaluation of Systemic Treatments for Advanced Melanoma: A Systematic Review

“…28,36,37 Cycle length varied from 1 week to 9 weeks, and was not reported in 5 studies. 27,32,33,37,38 The most common cycle length was 1 month (n = 4); half cycle correction was the exception rather than the rule (n = 1). Most studies were set in the United States (n = 8), with 5 from European countries, and 1 each from Canada and Australia.…”

“…Cost year was not stated in 3 studies. 37,38,40 One study obtained evidence for clinical inputs through a de novo systematic review and evidence synthesis process 41 ; 1 identified clinical evidence inputs through published systematic reviews. 28 For all remaining studies, no evidence of a systematic approach to the identification of clinical inputs was presented.…”

“…41 Six studies included only 1 comparator, using evidence from a single phase III clinical trial. [30][31][32]35,37,40 For the remaining studies, approaches to evidence synthesis were varied and sometimes unclear, 29 and included naïve comparison, 27,33,34,36,39 Bucher indirect comparison, 28 mixed covariate adjusted indirect comparisons using individual patient data, 38 and network metaanalysis. 41 Most commonly, PFS and OS outcomes from clinical trials were the source of treatment effects in the studies (n = 13).…”

“…32 Extrapolation of OS curves used external data sources (eg, cancer registries, long-term follow-up of ipilimumab trials) in a number of the studies to capture the natural history of the disease. 28,30,31,38 Only 1 study reported adjusting the OS data for treatment crossover. 28 With 1 exception, 37 studies did not consider the suitability of parametric modeling or explore alternative options.…”

Possibilities of Improving the Clinical Value of Immune Checkpoint Inhibitor Therapies in Cancer Care by Optimizing Patient Selection

“…Cost-effectiveness analysis has been carried out in numerous indications for ICIs yielding cost-effectiveness in some indications with a high willingness-to-pay (WTP) threshold [141]. With a WTP threshold of $100,000/QALY, the first line monotherapy studies have shown the cost-effectiveness of the therapy in melanoma (nivolumab/pembrolizumab vs. dacarbazine/ipilimumab [142][143][144][145]) and in NSCLC PD-L1 ≥50% (pembrolizumab vs. chemotherapy [146]). Conversely, none of the combinations tested in NSCLC (pembrolizumab+chemotherapy vs. chemotherapy [147] or atezolizumab+bevazicumab+chemotherapy vs. bevazicumab+chemotherapy [148]) or melanoma (nivolumab-ipilimumab vs. nivolumab [149]) were cost-effective with ICER of $147,366-454,092/QALY.…”