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Prognostic Implication of KRAS G12C Mutation in a Real-World KRAS-Mutated Stage IV NSCLC Cohort Treated With Immunotherapy in The Netherlands.


ABSTRACT:

Introduction

With the approval of G12C inhibitors as the second line of treatment for KRAS G12C-mutated NSCLC, and the expanding research regarding targeting KRAS, it is key to understand the prognostic implication of KRAS G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV KRAS G12C-mutated NSCLC to those with a KRAS non-G12C mutation in a first-line setting of (chemo)immunotherapy.

Methods

This nationwide population-based study used real-world data from The Netherlands Cancer Registry. We selected patients with stage IV KRAS-mutated lung adenocarcinoma diagnosed in 2019 to 2020 who received first-line (chemo-)immunotherapy. Primary outcome was OS.

Results

From 28,120 registered patients with lung cancer, 1185 were selected with a KRAS mutation, of which 494 had a KRAS G12C mutation. Median OS was 15.5 months (95% confidence interval [CI]: 13.6-18.4) for KRAS G12C versus 14.0 months (95% CI:11.2-15.7) for KRAS non-G12C (p = 0.67). In multivariable analysis, KRAS subtype was not associated with OS (hazard ratio = 0.95, 95% CI: 0.82-1.10). For the subgroup with programmed death-ligand 1 at 0% to 49% who received chemoimmunotherapy, median OS was 13.3 months (95% CI: 10.5-15.2) for G12C and 9.8 months (95% CI: 8.6-11.3) for non-G12C (p = 0.48). For the subgroup with programmed death-ligand 1 more than or equal to 50% who received monoimmunotherapy, the median OS was 22.0 months (95% CI: 18.4-27.3) for G12C and 18.9 months (95% CI: 14.9-25.2) for non-G12C (p = 0.36).

Conclusions

There was no influence of KRAS subtype (G12C versus non-G12C) on OS in patients with KRAS-mutated stage IV NSCLC treated with first-line (chemo)immunotherapy.

SUBMITTER: Noordhof AL 

PROVIDER: S-EPMC10477684 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Prognostic Implication of <i>KRAS</i> G12C Mutation in a Real-World <i>KRAS</i>-Mutated Stage IV NSCLC Cohort Treated With Immunotherapy in The Netherlands.

Noordhof Anneloes L AL   Swart Esther M EM   Damhuis Ronald A M RAM   Hendriks Lizza E L LEL   Kunst Peter W A PWA   Aarts Mieke J MJ   van Geffen Wouter H WH  

JTO clinical and research reports 20230629 9


<h4>Introduction</h4>With the approval of G12C inhibitors as the second line of treatment for <i>KRAS</i> G12C-mutated NSCLC, and the expanding research regarding targeting <i>KRAS</i>, it is key to understand the prognostic implication of <i>KRAS</i> G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV <i>KRAS</i> G12C-mutated NSCLC to those with a <i>KRAS</i> non-G12C mutation in a first-line setting of (chemo)immunotherapy.<h4>Methods</h4>Th  ...[more]

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