First-Line Anaplastic Lymphoma Kinase (ALK) Inhibitors for ALK-Positive Lung Cancer in Asian Populations: Systematic Review and Network Meta-Analysis

Abstract

Various anaplastic lymphoma kinase inhibitors (ALKIs) have been approved for first-line use in treating anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). To date, no head-to-head comparison of these newer generation ALKIs has been made, and different efficacies of ALKIs may present across ethnicity. This study aims to compare newer generation ALKIs for treatment efficacy in Asian groups using network meta-analysis. Phase II/III trials that enrolled treatment-naïve Asian ALK-rearranged NSCLC patients treated by ALKIs were included. Progression-free survival (PFS) and overall response rate (ORR) of each trial were extracted as indicators of drug efficacy. Surfaces under cumulative ranking curves (SUCRAs) were calculated as a numeric presentation of the overall ranking associated with each agent. After a systematic literature review, six phase III clinical trials were included. Our results showed that newer generation ALKIs, such as alectinib, brigatinib, ensartinib, and lorlatinib, all demonstrated superior efficacy to crizotinib. Among those, ensartinib exhibited the best overall SUCRA value and ranked first among all agents. According to our network meta-analysis, ensartinib may currently be the most effective first-line treatment for Asian patients with ALK-positive NSCLC. However, this conclusion needs further validation by a larger scale of clinical trials or posthoc analysis of Asian populations. Moreover, in our comparison, low-dose alectinib (300 mg twice daily) exhibited an efficacy profile similar to a higher dose regimen in Asian populations.