A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer

Background: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are mainly used in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), but a comprehensive clinical evaluation of ALK-TKIs is lacking. Hence, a comparison of ALK-TKIs for first-line treatment of ALK-positive advanced NSCLC is essential to provide rational drug use and a basis for improving national policies and systems. Methods: According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs (2021) and the Technical Guideline for the Clinical Comprehensive Evaluation of Antitumor Drugs (2022), a comprehensive clinical evaluation index system of first-line treatment drugs for ALK-positive advanced NSCLC was established by literature review and expert interviews. We conducted a systematic literature review, meta-analysis, and other relevant data analyses, combined with an indicator system, to establish a quantitative and qualitative integration analysis for each indicator and each dimension of crizotinib, ceritinib, alectinib, ensartinib, brigatinib, and lorlatinib. Results: The comprehensive clinical evaluation results of all dimensions were as follows: in terms of safety, alectinib had a lower incidence of grade 3 and above adverse reactions; for effectiveness, alectinib, brigatinib, ensartinib, and lorlatinib showed better clinical efficacy, and alectinib and brigatinib have been recommended by several clinical guidelines; in terms of economy, second-generation ALK-TKIs have more cost-utility advantages, and both alectinib and ceritinib have been recommended by the UK and Canadian Health Technology Assessment (HTA) agencies; for suitability, accessibility, and innovation, alectinib has a higher degree of physician recommendations and patient compliance. Except for brigatinib and lorlatinib, all other ALK-TKIs have been admitted to the medical insurance directory; the accessibility of crizotinib, ceritinib, and alectinib is good, meeting the needs of patients. Second- and third-generation ALK-TKIs have higher blood-brain barrier permeability, stronger inhibition ability, and innovation than first-generation ALK-TKIs. Conclusions: Compared with other ALK-TKIs, alectinib performs better across six dimensions and has a higher comprehensive clinical value. The results provide better drug choice and rational use for patients with ALK-positive advanced NSCLC.