Prevalence of Genomic Alterations in <i>EGFR</i>, <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Among Early-Stage Nonsquamous Non-Small Cell Lung Cancer in Brazil.

Abstract

We studied the prevalence of somatic mutations in <i>EGFR, KRAS, BRAF,</i> and <i>NRAS</i> among Brazilian patients with early-stage non-small cell lung cancer (NSCLC). We also explored the association between these mutations and clinicopathologic characteristics. We screened 557 patients diagnosed with NSCLC who underwent <i>EGFR</i>, <i>KRAS</i>, <i>BRAF</i>, and <i>NRAS</i> gene sequencing by next-generation sequencing (NGS) or RT-PCR (<i>EGFR</i> only) between 2021 and 2023. We analyzed the frequency of mutations in these genes and their association with clinical characteristics among 399 patients with early-stage nonsquamous NSCLC. Among 399 patients with early-stage nonsquamous NSCLC included in the analysis, we identified mutations in 218 (54.6%), totaling 224. The median age was 67 years, and most were female (58.9%). The most frequently mutated genes were <i>EGFR</i> and <i>KRAS</i>. Actionable genomic alterations were found in 137 cases, representing 34.3% of the entire cohort and 62.8% of patients with mutations. In cases with actionable mutations identified by NGS, <i>EGFR</i> mutations accounted for 68.0%, followed by <i>KRAS</i> (27.3%) and <i>BRAF</i> (4.7%). We found a significant association between histologic subtype and grade, as well as between tumor T stage and histologic subtype. A higher frequency of <i>EGFR</i> mutations was observed among females. We noted an association between mutated <i>EGFR</i> and the lepidic subtype, mutated <i>KRAS</i> and the mucinous/colloid subtype, and between the nonmutated genotype and the solid/micropapillary subtype. This study provides an overview of the genomic landscape of early-stage nonsquamous NSCLC in Brazilian patients. The high prevalence of mutations observed in our cohort underscores the importance of genomic testing in this setting, enabling selection of patients suitable for targeted approved therapies or clinical trials.