Economic evaluation crizotinib, alectinib and brigatinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC).

Abstract

e20714 Background: Crizotinib and alectinib are approved as 1st and brigatinib as 2nd line (post crizotinib) therapy for ALK+ NSCLC. Alectinib and brigatinib are more expensive but potentially clinically more beneficial in terms of progression free survival (PFS). We performed cost-effectiveness/utility analyses based on published PFS data. Methods: The Bücher method was used to indirectly estimate comparative PFS hazard ratios (HR) for PFS between the 3 agents. A 2-state Markov model (progression, death) was specified, PFS survival curves were digitized, and Weibull distributions fitted with life time horizon. Drug costs were per RedBook (US$ 2018). Cost of adverse event management, disease progression and follow up were per published data. Outcomes included PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Incremental cost effectiveness/utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained were estimated. Deterministic results were verified by probabilistic sensitivity analyses (PSA). Analyses were from the US payer perspective. Results: In indirect comparisons, alectinib (HR 0.47, 95%CI 0.34-0.65) and brigatinib (HR 0.49, 95%CI 0.33-0.74) were superior, but equivalent to each other (HR 1.04, 95%CI 0.62-1.75), in PFS over crizotinib in their respective lines. Deterministic (probabilistic) PFSLY, PFSQALY and cost estimates were 0.86 (0.91), 0.54 (0.57) and $193,544 ($203,881) for crizotinib; 1.27 (1.36), 0.80 (0.85) and $236,279 ($251,183) for alectinib; 1.25 (1.33), 0.79 (0.83) and $492,681 ($522,533) for brigatinib. See Table for deterministic (probabilistic) ICER/ICUR results ($ in parentheses denote savings). Conclusions: In this independent economic evaluation not considering intracranial metastasis, brigatinib had the highest life time cost compared to alectinib and crizotinib (all drugs as approved). Comparable gains in PFSLY and PFSQALY for brigatinib can be achieved with alectinib at lower cost, making alectinib the most cost-effective treatment option for ALK+ NSCLC. [Table: see text]