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September 10, 2025

KRAS mutation subtypes in metastatic non-small cell lung cancer

Key Points

No significant differences in clinical or survival metrics were found between KRAS G12C and non-G12C subtypes.
Median overall survival was similar, with 14.46 months for KRAS G12C and 15.36 months for non-G12C, suggesting similar treatment challenges.
The study included 101 patients and used next generation sequencing to confirm KRAS mutations for a comparative analysis.
Understanding these KRAS subtypes may provide insights for better-targeted therapies, as similar response rates were observed.

Abstract

The aim of this study is to determine the clinicopathologic features of KRAS mutant metastatic non-small cell lung cancer (NSCLC) patients and to determine the clinical, prognostic and survival differences between subtypes and their relationship with response to treatment. A total of 101 patients with KRAS mutant metastatic non-small cell lung cancer treated in 3 oncology centers between 2013 and 2024 were included in this retrospective, multicenter study conducted in Turkey. Molecular analysis was confirmed by next generation sequencing (NGS; QIAGEN Clinical Insight Interpretation, United States). The Kaplan-Meier method was used to compare progression-free (PFS) and overall survival (OS) times between KRAS subgroups. KRAS G12C mutation was detected in 69 (68.3%) and KRAS non-G12C mutation in 32 (31.7%) patients. In both groups, the majority of patients were male (91.3% vs. 84.4%), smokers or former smokers (92.8% vs. 90.6%) and histologically had adenocarcinoma subtype (88.4% vs. 81.3%). There was no statistically significant difference in PD-L1 expression (21.7% vs. 34.4%, P: 0.132). In the KRAS non-G12C group, the most common mutations were G12V 15 (14.8%) and G12D 6 (5.9%). The most common co-mutation accompanying KRAS G12C mutation was TP53 (23%), while the most common co-mutation accompanying KRAS non-G12C was Rictor (36.3%). While 23 (33.3%) patients with KRAS G12C mutation developed brain metastasis, this rate was 14 (43.8%) in the KRAS non-G12C mutation group (P=0.312). Median follow-up was 15.30 (0.3-112.0) months. The objective response rate (ORR) with first-line treatment was 47.5% in the KRAS G12C group and 48.3% in the KRAS non-G12C group (P: 0.657). Median PFS was 4.46 (2.85-6.08) months in the KRAS G12C group and 5.23 (3.46-6.99) months in the KRAS non-G12C group (P: 0.852). Median overall survival was 14.46 (8.34-20.58) months in the KRAS G12C group and 15.36 (5.01-25.71) months in the KRAS non-G12C group (P: 0.201). In KRAS mutant metastatic NSCLC patients, no significant difference was found between KRAS subtypes (G12C vs. non-G12C) in terms of clinical, prognostic and survival data.

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