Treatment with Next-Generation ALK Inhibitors Fuels Plasma ALK Mutation Diversity.

ABSTRACT:

Purpose

Acquired resistance to next-generation ALK tyrosine kinase inhibitors (TKIs) is often driven by secondary ALK mutations. Here, we investigated utility of plasma genotyping for identifying ALK resistance mutations at relapse on next-generation ALK TKIs.

Experimental design

We analyzed 106 plasma specimens from 84 patients with advanced ALK-positive lung cancer treated with second- and third-generation ALK TKIs using a commercially available next-generation sequencing (NGS) platform (Guardant360). Tumor biopsies from TKI-resistant lesions underwent targeted NGS to identify ALK mutations.

Results

By genotyping plasma, we detected an ALK mutation in 46 (66%) of 70 patients relapsing on a second-generation ALK TKI. When post-alect

SUBMITTER: Dagogo-Jack I 

PROVIDER: S-EPMC6858956 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature