MET and NF2 alterations confer primary and early resistance to first-line alectinib treatment in ALK-positive non-small-cell lung cancer.

ABSTRACT: Although first-line alectinib has prolonged survival in ALK-mutated non-small-cell lung cancers (NSCLCs), the response to treatment varies among patients, and the primary/early development of alectinib resistance mechanisms is still not fully understood. Here, we analyzed molecular profiles of 108 alectinib-treated patients (first-line and second-line after crizotinib) with confirmed relapse by targeted sequencing of cancer-related genes. After first-line treatment, off-target MET and NF2 alterations were more frequent than on-target alterations within the first 6 months, causing primary or early resistance. Conversely, on-target alterations became prevalent after 1 year of first-line alectinib treatment and predominantly after second-line. The incidence of acquired resistance also depende

SUBMITTER: Hu J 

PROVIDER: S-EPMC12420365 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature