Dissecting the Clinical Characteristics and Treatment Outcomes Correlates of KRAS G12C-Mutated Non-Small Cell Lung Cancer

Yawan Jing,1,2 Ruixin Cheng,3 Hao Zeng,1 Qin Huang,1 Dongyu He,1 Jiayi Sun,1 Panwen Tian,1,4 Yalun Li1,4 1Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Center/Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Gerontology and Geriatrics, Tibet Autonomous Region People’s Hospital, Lhasa, Tibet Autonomous Region, People’s Republic of China; 3Department of Radiation Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 4Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Yalun Li; Panwen Tian, Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86 28 85423660, Email [email protected]; [email protected]: KRAS mutation is one of the most common driver oncogenes in non-small cell lung cancer (NSCLC), and the most common mutation subtype is G12C. However, there is still a lack of efficacy and prognosis data related to immunotherapy, which hinders the promotion of new strategies.Methods: Clinical characteristics and treatment outcomes were collected and analyzed for patients with NSCLC harboring KRAS mutations at West China Hospital of Sichuan University from June 2013 to March 2023.Results: Among the 231 patients with KRAS-mutated NSCLC, 29.4% had KRAS G12C mutations. Compared to the KRAS non-G12C NSCLC group, the KRAS G12C NSCLC group had a greater number of pack-years. The programmed death ligand 1 expression and the proportion of patients with a high tumor mutational burden were not significantly different between the two groups. Similar patterns of TP53, STK11, and CDKN2A mutations were observed between KRAS G12C and KRAS non-G12C NSCLC groups. The median progression-free survival (PFS) (8.4 vs 7.0 months, p=0.100) and overall survival (OS) (12.1 vs 18.1 months, p=0.590) were not statistically different between KRAS G12C and KRAS non-G12C. Compared to patients with KRAS G12C NSCLC who did not receive immunotherapy, patients who received immunotherapy had a better objective response rate (46.2% vs 0%, p=0.002), PFS (12.2 vs 7.5 months, p=0.087) and OS (49.9 vs 11.1 months, p=0.12).Conclusion: Patients with KRAS G12C were more likely to be smokers. Advanced KRAS G12C NSCLC patients who received immunotherapy had a better ORR than those who did not, suggesting that patients with G12C mutations are more likely to benefit from immunotherapy.Keywords: non-small cell lung cancer, KRAS G12C mutation, KRAS mutation, immunotherapy, overall survival