Non-Small Cell Lung Cancer Coverage from Every Angle

SITC 2021: Prevalence of KRAS mutations in Advanced Nonsquamous NSCLC

By: Julia Fiederlein
Posted: Monday, November 29, 2021

Marina Chiara Garassino, MD, of the University of Chicago Medicine and Biological Sciences, and colleagues conducted a study to assess the prevalence of KRAS mutations in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) who were treated with first-line pembrolizumab. This pooled analysis of the phase III KEYNOTE-042 and KEYNOTE-189 trials, which was presented during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 364) and published in the Journal for ImmunoTherapy of Cancer, also examined the relationship of such mutations with select patient characteristics.

KRAS G12C mutations occurred with moderate frequency in patients with nonsquamous NSCLC, with most occurring in current or former smokers,” the investigators commented. “[These] mutations occurred at higher frequency in patient subgroups defined by higher tissue tumor mutation burden and PD-L1 tumor proportion score.”

A total of 590 patients were included in the analysis (KEYNOTE-042: n = 301; KEYNOTE-189: n = 289). The investigators performed whole-exome sequencing of tumor tissue and matched normal DNA samples. A standardized immunohistochemistry assay was used to evaluate the PD-L1 tumor proportion score. The prevalence of KRAS mutations and their relationships with tumor mutation burden, PD-L1 tumor proportion scores, and smoking status were analyzed descriptively.

Mutations of KRAS G12C, G12D, and G12V were reported in 11%, 4.1%, and 5.4% of patients, respectively. According to the investigators, KRAS G12C mutations were detected almost exclusively in current or former smokers. Tumors with a tissue tumor mutation burden of at least 175 mutations per exome or a PD-L1 tumor proportion score of at least 50% were enriched with KRAS G12C mutations; the prevalence seemed to be highest in patients with tumors harboring both these characteristics.

Disclosure: No information regarding conflicts of interest was provided.

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