@article{3102356,
    title = "Prognostic Impact of KRAS G12C Mutation in Patients With NSCLC: Results From the European Thoracic Oncology Platform Lungscape Project",
    author = "Finn, S.P. and Addeo, A. and Dafni, U. and Thunnissen, E. and Bubendorf, L. and Madsen, L.B. and Biernat, W. and Verbeken, E. and Hernandez-Losa, J. and Marchetti, A. and Cheney, R. and Warth, A. and Speel, E.-J.M. and Quinn, A.M. and Monkhorst, K. and Jantus-Lewintre, E. and Tischler, V. and Marti, N. and Dimopoulou, G. and Molina-Vila, M.A. and Kammler, R. and Kerr, K.M. and Peters, S. and Stahel, R.A. and European Thoracic Oncology Platform Lungscape Investigators",
    journal = "Journal of Thoracic Oncology",
    year = "2021",
    volume = "16",
    number = "6",
    pages = "990-1002",
    publisher = "HANLEY & BELFUS-ELSEVIER INC",
    issn = "1556-0864, 1556-1380",
    doi = "10.1016/j.jtho.2021.02.016",
    keywords = "adagrasib;  cytosine;  guanine;  sotorasib;  KRAS protein, human;  piperazine derivative;  protein p21;  pyridine derivative;  pyrimidine derivative;  sotorasib, adult;  aged;  Article;  cancer chemotherapy;  cancer patient;  cancer prognosis;  cancer radiotherapy;  cancer recurrence;  cancer staging;  cancer surgery;  cohort analysis;  confidence interval;  controlled study;  Europe;  European;  female;  follow up;  gene mutation;  hazard ratio;  histology;  human;  major clinical study;  male;  microfluidics;  multiplex polymerase chain reaction;  non small cell lung cancer;  oncogene K ras;  overall survival;  prevalence;  recurrence free survival;  genetics;  lung tumor;  mutation;  prognosis;  tumor recurrence, Humans;  Lung Neoplasms;  Mutation;  Neoplasm Recurrence, Local;  Piperazines;  Prognosis;  Proto-Oncogene Proteins p21(ras);  Pyridines;  Pyrimidines",
    abstract = "Introduction: KRAS mutations, the most frequent gain-of-function alterations in NSCLC, are currently emerging as potential predictive therapeutic targets. The role of KRAS-G12C (Kr_G12C) is of special interest after the recent discovery and preclinical analyses of two different Kr_G12C covalent inhibitors (AMG-510, MRTX849). Methods: KRAS mutations were evaluated in formalin-fixed, paraffin-embedded tissue sections by a microfluidic-based multiplex polymerase chain reaction platform as a component of the previously published European Thoracic Oncology Platform Lungscape 003 Multiplex Mutation study, of clinically annotated, resected, stage I to III NSCLC. In this study, -Kr_G12C mutation prevalence and its association with clinicopathologic characteristics, molecular profiles, and postoperative patient outcome (overall survival, relapse-free survival, time-to-relapse) were explored. Results: KRAS gene was tested in 2055 Lungscape cases (adenocarcinomas: 1014 [49%]) with I or II or III stage respective distribution of 53% or 24% or 22% and median follow-up of 57 months. KRAS mutation prevalence in the adenocarcinoma cohort was 38.0% (95% confidence interval (CI): 35.0% to 41.0%), with Kr_G12C mutation representing 17.0% (95% CI: 14.7% to 19.4%). In the “histologic-subtype” cohort, Kr_G12C prevalence was 10.5% (95% CI: 9.2% to 11.9%). When adjusting for clinicopathologic characteristics, a significant negative prognostic effect of Kr_G12C presence versus other KRAS mutations or nonexistence of KRAS mutation was identified in the adenocarcinoma cohort alone and in the “histologic-subtype” cohort. For overall survival in adenocarcinomas, hazard ratio (HR)G12C versus other KRAS is equal to 1.39 (95% CI: 1.03 to 1.89, p = 0.031) and HRG12C versus no KRAS is equal to 1.32 (95% CI: 1.03 to 1.69, p = 0.028) (both also significant in the “histologic-subtype” cohort). For time-to-relapse, HRG12C versus other KRAS is equal to 1.41 (95% CI: 1.03 to 1.92, p = 0.030). In addition, among all patients, for relapse-free survival, HRG12C versus no KRAS is equal to 1.27 (95% CI: 1.04 to 1.54, p = 0.017). Conclusions: In this large, clinically annotated stage I to III NSCLC cohort, the specific Kr_G12C mutation is significantly associated with poorer prognosis (adjusting for clinicopathologic characteristics) among adenocarcinomas and in unselected NSCLCs. © 2021 International Association for the Study of Lung Cancer"
}