Impact of KRAS Mutations on Clinical Outcomes of Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer Receiving Anti-PD-1/PD-L1 Therapy

• Published in: Targeted oncology 2023-01, Vol.18 (1), p.129-138
• Main Authors: Veccia, Antonello, Dipasquale, Mariachiara, Kinspergher, Stefania, Monteverdi, Sara, Girlando, Salvatore, Barbareschi, Mattia, Caffo, Orazio
• Format: Article
• Language: English
• Subjects: B7-H1 Antigen - immunology; B7-H1 Antigen - therapeutic use; Biomedicine; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - therapy; Chemotherapy; Clinical outcomes; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - therapy; Medicine; Medicine & Public Health; Mutation; Oncology; Original; Original Research Article; Proto-Oncogene Proteins p21(ras) - genetics; Retrospective Studies; Treatment Outcome
• ISSN: 1776-2596; 1776-260X
• DOI: 10.1007/s11523-022-00934-6

Background KRAS is the most frequently mutated gene in non-small cell lung cancer (NSCLC), however conflicting data are available on its role as a biomarker. Objective The aim of our work was to investigate the impact of KRAS mutations on response and survival outcomes in advanced non-squamous NSCLC patients treated with immune checkpoint inhibitors alone or in combination with chemotherapy. Patients and Methods We retrospectively identified 119 patients, most of whom (58%) were KRAS wild type. For each patient we evaluated overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). An exploratory analysis was performed among KRAS mutated patients to investigate the impact of specific KRAS mutations on response and survival outcomes. Results After a median follow-up of 10.3 months, the median OS was 14.9 months (95% confidence interval [CI] 7.6–22.7) in wild-type KRAS patients versus 14.7 months (95% CI 8.0–19.5) in mutated KRAS patients ( p  = 0.529). No differences were detected between the two groups in terms of PFS and DCR. Patients with a KRAS G12C mutation reported survival and response outcomes that were not statistically different from those of patients with other KRAS mutations. Conclusion Our data confirmed that KRAS mutational status is not associated with survival and response outcomes in advanced non-squamous NSCLC patients treated with immunotherapy alone or combined with chemotherapy.