Therapeutic Outcomes and Clinical Features of Advanced Non–Small Cell Lung Cancer Carrying KRAS Mutations: A Multicenter Real-life Retrospective Study

• Published in: Clinical lung cancer 2022-11, Vol.23 (7), p.e478-e488
• Main Authors: Mazzaschi, Giulia, Perrone, Fabiana, Minari, Roberta, Verzè, Michela, Azzoni, Cinzia, Bottarelli, Lorena, Pluchino, Monica, Armillotta, Maria Pia, Ubaldi, Annalisa, Altimari, Annalisa, Gruppioni, Elisa, Sperandi, Francesca, Andrini, Elisa, Guaitoli, Giorgia, Bettelli, Stefania, Longo, Lucia, Bertolini, Federica, Barbieri, Fausto, Pagano, Maria, Bonelli, Candida, Tagliavini, Elena, Nicoli, Davide, Ubiali, Alessandro, Zangrandi, Adriano, Trubini, Serena, Proietto, Manuela, Gnetti, Letizia, Tiseo, Marcello
• Format: Article
• Language: English
• Subjects: B7-H1 Antigen - genetics; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Clinico-pathological correlations; G12C; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mutation - genetics; non-G12C; Observational study; Proto-Oncogene Proteins p21(ras) - genetics; Retrospective Studies; Treatment Outcome
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2022.07.005

•Kirsten Rat Sarcoma (KRAS)-targeting agents are revolutionizing the treatment landscape of advanced non–small-cell lung cancer (NSCLC).•Real-life data on KRAS-mutant NSCLC represent an urgent need.•Our multicenter study on 297 KRAS-mut NSCLC involves the largest Italian cohort.•No clinically significant differences between KRAS G12C versus non-G12C were observed•A worse prognosis characterized chemo-treated KRAS-mut NSCLC compared to IT-treated Targeting Kirsten Rat Sarcoma (KRAS) has been deemed impossible for long time, but new drugs have recently demonstrated promising results. Evidence on the outcome of KRAS-mutant advanced-NSCLC treated with new standard regimens are still scarce. Thus, we aimed at assessing the incidence and clinical impact of KRAS mutations in a real-life population of advanced-NSCLC, exploring the prognostic significance of distinct alterations. The present multicenter retrospective study, conducted by 5 Italian Centers from January 2018 to February 2020, involved 297 advanced KRAS mutant NSCLC. Complete clinico-pathological data were evaluated. Out of 297 patients, 130 carried KRAS_G12C mutation, while 167 presented with mutations other than G12C. Within KRAS_non-G12C group, 73%, 16.8% and 8.9% harboured G12X, codon 13 and Q61H alterations, respectively. No significant differences in survival outcome and treatment response were documented according to KRAS_G12C versus non-G12C, nor KRAS_G12C versus G12X versus other mutations. On univariate analysis ECOG PS, number and sites of metastatic lesions and PD-L1 status significantly impacted on survival. A clear trend towards worse prognosis was apparent in chemotherapy-treated patients, while immunotherapy-based regimens were associated to prolonged survival. Investigating the outcome of PD-L1 ≥ 50% population, we did not detect any significant difference between KRAS_G12C and non-G12C subsets. Here, we report on real-life data from a large retrospective cohort of advanced NSCLC harbouring KRAS alterations, with particular attention to G12C mutation. Our study offers useful clues on survival outcome, therapeutic response and clinico-pathological correlations in KRAS-mutant setting, especially in the upcoming era of KRAS G12C targeting therapy. Kirsten Rat Sarcoma (KRAS) targeting-drugs revolution prompted us to conduct a retrospective study on 297 KRAS-mutant NSCLC assessing the clinical impact of KRAS mutations. No differences in survival and treatment outcomes were documented accord