According to results of an exploratory analysis, 50% of patients with ALK gene fusion–positive advanced non-small cell lung cancer (NSCLC) also characterized by 1 or more ALK resistance mutations to crizotinib responded to treatment with alectinib.1
Although alectinib, a small-molecule tyrosine kinase inhibitor, is currently approved by the US Food and Drug Administration (FDA) for the treatment of all patients with metastatic ALK-positive NSCLC,2 its initial FDA approval in 2015 was based on the results of 2 single-arm phase 2 clinical trials showing benefit in adult patients with ALK gene fusion-positive advanced NSCLC who had experienced disease progression on crizotinib.
In this study, next-generation sequencing was performed on available specimens of circulating tumor cell-free DNA (ctDNA) collected from patients enrolled in those 2 studies following progression on crizotinib but prior to treatment with alectinib (187 individuals) and postprogression on alectinib (48 individuals).
Of the 187 patients in the former group, single-nucleotide variants in ALK were detected in 48 patients (25.7%). The baseline characteristics were similar, including central nervous system lesions of those with and without point mutations in ALK, with exceptions including race and performance status. Compared with the subgroup without ALK mutations, there were higher percentages of patients in the ALK mutation subgroup of Asian race (33.3% vs 17.3%), and a performance status of 1 or higher (81.3% vs 64.1%).
Notably, 34 different ALK point mutations were identified in the ALK mutation subgroup, with specimens from 35% and 67% characterized by more than 1 ALK mutation and a known ALK resistance mutation to crizotinib, respectively.
This article originally appeared on Cancer Therapy Advisor