Abstract

e21102 Background: Crizotinib was approved by the FDA (2011) as the first ALK inhibitor for ALK+ NSCLC as the first line drug. This was followed by the approval as second line treatment of ceritinib (2014), alectinib (2015) and brigatinib (2017); and, following more data, now also as first line therapies in ALK+ NSCLC. With varying costs and clinical benefits for progression free survival (PFS), cost effectiveness/utility analyses were conducted. Methods: A 3 state Markov model was built including progression free, progression and death. PFS and overall survival curves were digitized and exponential functions were fit the curves for extrapolation beyond trial follow up. A lifetime horizon, US payer perspective, and a discount rate of 3% were applied. Drug costs were based on Redbook Wholesale Acquisition Cost while costs of adverse events, monitoring, disease progression were from literatures (US$ 2020). Adverse events reported at > 5% were included. Crizotinib was used as reference treatment. PFS life years (PFSLY), quality adjusted life years (PFSQALY), incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) were estimated in base case (BCA) and probabilistic sensitivity analyses (PSA). Results: Crizotinib was the reference drug in the following estimations. For alectinib, at incremental cost of $7,789 (PSA $7,719), the incremental PFSLY of 1.10 (1.10) and PFSQALY 1.07 (1.07) yielded an ICER of $7,109 ($7,030) / PFSLYG and an ICUR of $7,278 ($7.197) / PFSQALYG. For ceritinib, at incremental cost of $88,688 ($88,450), the incremental PFSLY of 1.02 (1.02) and PFSQALY of 1.01 (1.01) resulted in an ICER of $86,970 ($86,729) / PFSLYG and an ICUR of $87,472 / PFSQALYG. For brigatinib, at incremental cost of $84,680 ($83,986), the incremental PFSLY of 1.01 (1.01) and PFSQALY of 1.02 yielded an ICER of $83,774 ($83,073) / PFSLYG and an ICUR of $82,666 ($81,976) / PFSQALYG. Conclusions: Ceritinib had the highest lifetime cost and comparable PFSLY and PFSQALY to brigatinib. However, alectinib reported the highest PFSLY and PFSQALY gained while having lower costs than ceritinib and brigatinib, therefore being the most cost-effective treatment for naïve ALK+ NSCLC.[Table: see text]

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