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Updated: Aug 19, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Clinical outcomes of KRAS G12C versus non-G12C mutant NSCLC treated with immunotherapy: a multicentre real-world
Laura Masfarré1, Ana Sofia Parreira2, Natalia Castro3
1Medical Oncology, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain.
Background:
KRAS is the most heterogeneous and frequent oncogenic driver in non-small cell lung cancer (NSCLC). KRAS alleles and co-mutations shape the tumour microenvironment, potentially influencing benefit from immune checkpoint inhibitors (ICI). The aim of our study was to evaluate the patterns of KRAS mutations, their correlation with clinical and pathological features and their association with ICI outcomes.
Methods:
We conducted a multicentre retrospective analysis of patients with advanced KRAS-mutant NSCLC treated with ICI. Clinical, pathological and molecular data were collected, including KRAS mutation type (G12C vs non-G12C), key co-mutations and PD-L1 expression. These variables were correlated with clinical outcomes. Survival outcomes were analysed using Kaplan-Meier estimates and multivariate Cox regression models.
Results:
A total of 198 patients with KRAS mutant NSCLC were evaluated, with 49.5% carrying a G12C mutation. Overall, 81% of patients received first-line ICI, either as monotherapy or combined with chemotherapy. After a median follow-up of 48 months, G12C cases showed significantly longer median overall survival (OS) (15 vs 9 months; HR 0.71; p = 0.031). Multivariate analysis indicated that G12C mutations correlated with improved OS, as well as good performance status and absence of central nervous system (CNS) metastases.
Conclusions:
In this retrospective real-world cohort, KRAS mutation subtype was associated with differences in ICI outcomes, particularly OS. These findings should be considered hypothesis-generating and warrant prospective validation in molecularly characterized cohorts.
Insights
KRAS G12C mutations in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI) are linked to significantly longer overall survival (OS). This highlights the importance of KRAS mutation subtype in predicting ICI treatment outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- KRAS mutations are frequent oncogenic drivers in non-small cell lung cancer (NSCLC).
- Tumor microenvironment and co-mutations, influenced by KRAS alleles, may affect response to immune checkpoint inhibitors (ICI).
Purpose of the Study:
- To investigate KRAS mutation patterns in advanced NSCLC.
- To correlate KRAS mutations with clinical features and outcomes in patients receiving ICI therapy.
Main Methods:
- Multicenter retrospective analysis of 198 advanced KRAS-mutant NSCLC patients treated with ICI.
- Collected clinical, pathological, and molecular data, including KRAS G12C vs. non-G12C subtypes and PD-L1 expression.
- Analyzed survival outcomes using Kaplan-Meier estimates and multivariate Cox regression.
Main Results:
- 49.5% of patients harbored KRAS G12C mutations; 81% received first-line ICI.
- KRAS G12C-mutant NSCLC patients demonstrated significantly longer median overall survival (OS) (15 vs. 9 months; HR 0.71; p=0.031).
- Multivariate analysis confirmed G12C mutation as an independent predictor of improved OS, alongside good performance status and absence of CNS metastases.
Conclusions:
- KRAS mutation subtype significantly impacts ICI treatment outcomes, particularly OS, in NSCLC.
- Findings suggest KRAS G12C status is a crucial biomarker for predicting ICI efficacy.
- Prospective validation in molecularly characterized cohorts is warranted.