Alectinib, Brigatinib, and Lorlatinib As First-Line Therapies for Advanced ALK-Positive Non-Small Cell Lung Cancer: A Cost-Effectiveness Analysis

OBJECTIVES: Despite promising clinical trials, substantial treatment costs and the absence of head-to-head comparisons between alectinib, brigatinib, and lorlatinib have generated uncertainty regarding optimal first-line treatment for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). This study is the first to evaluate the cost-effectiveness of alectinib, brigatinib, and lorlatinib as first-line therapies for advanced ALK+ NSCLC from a US healthcare sector perspective.

METHODS: We developed a four-state partitioned survival model utilizing progression-free survival (PFS), intracranial progression-free survival (ICPFS), and overall survival (OS) 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 (CNS)-related progressed disease, non-CNS progressed disease, and death states over a 5-year horizon. Costs (2024 USD) included drug acquisition based on median of Department of Veteran Affairs (VA) and wholesale acquisition cost (WAC) prices, healthcare utilization, and adverse event management, all sourced from published literature. Quality-adjusted life years (QALYs) were derived using health utilities bootstrapped from these trials and adjusted for adverse events. Both deterministic and probabilistic sensitivity analyses were performed to evaluate uncertainty, alongside scenario analyses examining various pricing and efficacy specifications.

RESULTS: Over the model's 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 (ICERs) for alectinib and lorlatinib compared to 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 52% chance of being the cost-effective option, with alectinib at 37% and lorlatinib at 11%.

CONCLUSIONS: While alectinib and lorlatinib demonstrate enhanced efficacy, brigatinib emerges as the cost-effective first-line therapy for ALK+ NSCLC in the US at willingness-to-pay thresholds below $250,000/QALY.