KRAS mutation subtypes in metastatic non-small cell lung cancer

Ali Aytac; Bilgin Demir; Onur Yazdan Balcik; Tuba Ugur Tuzcu; Esin Oktay; Ibrahim Halil Erdogdu; Ozgur Tanriverdi; Ozan Yazici

doi:10.62347/GYHT4724

KRAS mutation subtypes in metastatic non-small cell lung cancer

Am J Cancer Res. 2025 Jul 15;15(7):3188-3196. doi: 10.62347/GYHT4724. eCollection 2025.

Authors

Ali Aytac¹, Bilgin Demir², Onur Yazdan Balcik³, Tuba Ugur Tuzcu⁴, Esin Oktay², Ibrahim Halil Erdogdu⁵, Ozgur Tanriverdi⁶, Ozan Yazici⁴

Affiliations

¹ Department of Medical Oncology, Mehmet Akif İnan Training and Research Hospital Sanlıurfa, Türkiye.
² Department of Internal Medicine, Division of Medical Oncology, Aydın Adnan Menderes University Faculty of Medicine Aydın, Türkiye.
³ Department of Medical Oncology, Alanya Alaaddin Keykubat University Hospital Alanya, Türkiye.
⁴ Department of Internal Medicine, Division of Medical Oncology Ankara Gazi University Faculty of Medicine Ankara, Türkiye.
⁵ Department of Molecular Pathology, Aydın Adnan Menderes University Faculty of Medicine Aydın, Türkiye.
⁶ Department of Internal Medicine, Division of Medical Oncology, Muğla Sıtkı Kocman University Muğla, Türkiye.

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.

Keywords: KRAS G12C; KRAS non-G12C; Non-small cell lung cancer; survival outcomes.