Abstract 4302: Molecular profile of KRAS G12C-mutant non-small-cell lung cancer and colorectal cancer in Brazilian patients

Background: Cancer is one of the leading causes of death and one of the main barriers to increasing life expectancy worldwide. The development of therapeutic strategies directly targeting mutant oncogenes, such as EGFR and BRAF, has resulted in substantial benefits for patients with a variety of cancers. KRAS is one of the most frequently mutated oncogenes, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) from Brazilian patients tested in a clinically-certified laboratory. Methodology: 4,842 NSCLC patients were tested for KRAS, NRAS, EGFR and BRAF mutations by next generation sequencing (NGS), while 4,815 CRC patients were tested for KRAS and NRAS mutations, by pyrosequencing, between 2017 and 2019 Results and Discussion: From the 4,842 NSCLC samples tested, KRAS G12 mutations were identified in 1013 cases (20.9%) and, 336 of these (6.9% of total) were KRAS G12C. Additionally, from 4,815 CRC samples tested, KRAS G12 mutations were identified in 1633 cases (33.9%), and 166 of these (3.4% of total) were KRAS G12C. In the literature, KRAS G12C has been reported in 14 to 16% of all lung adenocarcinomas, and 5% of colorectal adenocarcinomas. Our data illustrate a relevance of this mutation in a significant number of patients and highlight an opportunity for targeted therapy. Some studies characterizing lung cancers have indicated that KRAS mutations, including KRAS G12C, are mutually exclusive with other known oncogenic driver mutations in NSCLC. However, in the current analysis, we identified 30 cases of NSCLC harboring multiple mutations, such as KRAS G12C mutations co-existing with EGFR, BRAF or NRAS mutations. This finding is probably due to the multiclonal presentation in selected cases. Conclusions: A relatively high number of patients may present with KRAS G12C-mutant cancers in Brazil, indicating the relevance of identifying such cases for targeted therapy. Further studies will deepen the analysis of clonality and heterogeneity in this cohort. Citation Format: Bianca Mendes Souza, Laura Rabelo Leite, Sabrina A. Parma, Natalia P. Lopes, Frederico S. Malta, Luiz Henrique Araujo, Maira C. Freire. Molecular profile of KRAS G12C-mutant non-small-cell lung cancer and colorectal cancer in Brazilian patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4302.