Retrospective Study of Alectinib Treatment among Variants of ALK Fusion in Lung Adenocarcinoma

Background: Anaplastic lymphoma kinase (ALK) fusion genes are present in approximately 3-5% of nonsmall cell lung cancer (NSCLC) cases. Multiple echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion variants have been identified, with variants 1-3 (V1-3) accounting for approximately 90% of cases. However, clinical data on the efficacy of alectinib across these variants remain limited. In this study, we retrospectively evaluated the efficacy of alectinib treatment among ALK-fusion variants. Methods: We performed a retrospective analysis of patients treated with alectinib between January 2019 and December 2024. ALK-fusion variants were identified using Mutation Investigator using Next-era Sequencer (MINtS), a next-generation sequencing-based multigene mutation search system. Progressionfree survival (PFS), response rate, and overall survival (OS) were evaluated. Results: A total of 11 patients (male: n=4, female: n=7) were enrolled (V1: n=4, V2: n=3, V3: n=4); their median age was 75 years. Clinical stages at diagnosis were: stage II (n=1), and stage IV (n=10). Intrapulmonary metastasis was common in patients with V3. The median maximum tumor reduction rates were 90.5% (range, 84.0-92.0%), 63.4% (range, 35.0-84.0%), and 98.0% (range, 67.8-100.0%) for patients with V1, V2, and V3, respectively. The best overall response was partial response (PR) in all patients with V1 and V2. Three patients with V3 had complete response (CR) and one had PR. The median PFS was 16.5 and 15.9 months for patients with V1 and V2, respectively, and not reached for those with V3. Conclusions: In this study, there was no significant difference in the therapeutic effect of alectinib by ALK fusion variants. This finding indicates that alectinib may be an effective treatment option even for patients with V3.