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

Anneloes L Noordhof; Esther M Swart; Ronald A M Damhuis; Lizza E L Hendriks; Peter W A Kunst; Mieke J Aarts; Wouter H van Geffen

doi:10.1016/j.jtocrr.2023.100543

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

JTO Clin Res Rep. 2023 Jun 29;4(9):100543. doi: 10.1016/j.jtocrr.2023.100543. eCollection 2023 Sep.

Authors

Anneloes L Noordhof¹, Esther M Swart², Ronald A M Damhuis², Lizza E L Hendriks³, Peter W A Kunst⁴, Mieke J Aarts², Wouter H van Geffen¹

Affiliations

¹ Department of Respiratory Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands.
² Department of Research & Development, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands.
³ Department of Respiratory Medicine, GROW-School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands.
⁴ Department of Respiratory Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, 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.

Keywords: (Chemo-)immunotherapy; KRAS G12C; Kirsten rat sarcoma; Non–small cell lung cancer.