First-Line Alectinib, Brigatinib, and Lorlatinib for Advanced Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Cost-Effectiveness Analysis

Objectives To evaluate the cost-effectiveness of alectinib, brigatinib, and lorlatinib as first-line therapies for anaplastic lymphoma kinase-positive advanced non-small cell lung cancer from a US healthcare sector perspective. Methods We developed a 4-state partitioned survival model using progression-free survival, intracranial progression-free survival, and overall survival data from the ALEX, ALTA-1L, and CROWN clinical trials and published network meta-analyses. This model simulated patient transitions through progression-free, central-nervous-system-related progressed disease, non- central nervous system progressed disease, and death states over a 5-year horizon. Costs (2024 USD) included drug acquisition based on median of Department of Veteran Affairs and wholesale acquisition cost prices, healthcare utilization, and adverse events, all sourced from published literature. Quality-adjusted life years (QALYs) were derived using health utilities bootstrapped from these trials and adjusted for adverse events. We performed sensitivity and scenario analyses to evaluate uncertainty and explore various pricing and efficacy specifications. Results Over a 5-year horizon, alectinib cost $1 105 814 for 2.85 QALYs gained, brigatinib cost $1 059 283 for 2.66 QALYs gained, and lorlatinib cost $1 163 519 for 2.88 QALYs gained. Incremental cost-effectiveness ratios for alectinib and lorlatinib versus brigatinib were $245 536/QALY and $481 386/QALY, respectively. Probabilistic sensitivity analysis indicated that at a willingness-to-pay threshold of $150 000 per QALY, brigatinib had a 54% chance of being the cost-effective option, with alectinib at 36% and lorlatinib at 10%. Conclusions Although our model slightly favors brigatinib at a $150 000/QALY willingness-to-pay threshold, substantial uncertainty precludes definitive cost-effectiveness conclusions among the 3 first-line therapies.