OBJECTIVES: The study aimed to assess the cost-effectiveness of lorlatinib versus alectinib and brigatinib for the first-line treatment of adult patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small-cell-lung-cancer (NSCLC) from the Spanish National Health System perspective.

METHODS: A partitioned survival model comprising four health-states (pre-progression, non-intracranial-progression, intracranial-progression, and death) was used to estimate, in monthly cycles, the costs and outcomes (in terms of life-years-gained [LYG] and quality-adjusted-life-years [QALYs]) accumulated over a lifetime horizon. Overall survival and progression-free survival were derived from the CROWN study for lorlatinib, and from a network meta-analysis of randomized controlled trials for alectinib and brigatinib. Utilities reflected EQ-5D-5L data obtained in the CROWN study for lorlatinib, ALEX study for alectinib and ALTA-1L study for brigatinib. Total costs (expressed in euros using a 2021 cost year) included drug-acquisition, subsequent-treatment, disease-management, adverse-event management, and end-of-life care. Unitary costs were derived from local databases and literature. A 3% discount rate was applied for costs and outcomes. Deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed.

RESULTS: Lorlatinib provided higher LYG (7.40) and QALY gained per patient (5.89) than alectinib (6.69 LYG/patient and 4.46 QALYs/patient) and brigatinib (5.66 LYG/patient and 3.59 QALYs/patient). The lifetime total costs accounted €268,827/patient with lorlatinib, versus €278,066 with alectinib and €232,200 with brigatinib. Lorlatinib resulted a dominant option (more effective and less costly) compared to alectinib. The incremental cost-utility ratio (ICUR) was €15,912/QALY gained with lorlatinib versus brigatinib. In the DSA, time horizon and utility values showed the greatest impact on cost-effectiveness. In the PSA, alectinib was extendedly dominated by lorlatinib and the mean ICUR of lorlatinib versus brigatinib resulted in €18,508/QALY gained.

CONCLUSIONS: Lorlatinib dominated alectinib and was a cost-effective option versus brigatinib, assuming a willingness-to-pay threshold of €25,000/QALY, for the treatment of ALK+ advanced NSCLC in Spain.