Abstract
BACKGROUND: In Latin America, lung cancer is the leading cause of cancer-related death. Oncogenic driver alterations, including EGFR, KRAS, and ALK, are key therapeutic targets with a demonstrated impact on survival and disease progression. However, genetic heterogeneity may influence clinical outcomes and prognosis, and there is a notable lack of synthesized data on these factors in Hispanic or Latino populations. This review aimed to evaluate the prognostic relationship between genetic alterations and targeted therapies with overall survival (OS) and progression-free survival (PFS) in Latin American patients with non-small cell lung cancer (NSCLC). METHODS: We conducted a systematic literature review of publications and abstracts until June 2024 including observational studies performed with NSCLC Latin population that evaluate the prognostic impact of molecular alterations on survival and progression. RESULTS: We analyzed 47 studies (21,046 patients) reporting the clinical impact of actionable and non-actionable mutations on prognosis. The mean age was 60.5 years, 52.5% were women. Patients treated with first-generation EGFR-tyrosine kinase inhibitors (TKIs) had a PFS benefit [hazard ratio (HR) =0.75; 95% confidence interval (CI): 0.61-0.91], while second-generation EGFR-TKIs showed an OS benefit (HR =0.64; 95% CI: 0.54-0.76) compared to chemotherapy. Common EGFR mutations had a lower risk of mortality. Patients with KRAS mutations had shorter median OS and PFS compared to those with EGFR mutations (P<0.001). CONCLUSIONS: Latino patients with EGFR-mutated NSCLC treated with targeted therapy show improved OS and lower progression risk, especially with second-generation EGFR-TKIs, compared to wild-type (WT) patients on chemotherapy. KRAS mutations had the poorest outcomes. Increased Latino representation in lung cancer trials is essential to address evidence disparities.