Impact of Co-mutations and Transcriptional Signatures in Non-Small Cell Lung Cancer Patients Treated with Adagrasib in the KRYSTAL-1 Trial.

ABSTRACT:

Purpose

KRAS inhibitors are revolutionizing the treatment of non-small cell lung cancer (NSCLC), but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Experimental design

Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib [KRYSTAL-1 (NCT03785249)] were included in the analysis. Pretreatment next-generation sequencing data were collected per protocol. HTG EdgeSeq Transcriptome Panel was used for gene expression profiling. Clinical endpoints included objective response, progression-free survival (PFS), and overall survival (OS). KRASG12C-mutant NSCLC cell lines and xenograft models were used for sensitivity analyses and combination drug screens.

Results

KEAP1 MUT and STK11MUT were associated with shorter survival to adagr

SUBMITTER: Negrao MV 

PROVIDER: S-EPMC11911804 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature