Abstract 6158: Tumor genomic heterogeneity in non-small cell lung cancer (NSCLC) patients from Latin America

Abstract Motivation: Life prospects of non-small cell lung cancer (NSCLC) patients have greatly improved over the last decades with the adoption of tumor genomic profiling. A better understanding of the mutational landscape has allowed for a more precise molecular characterization and the development of more effective treatment alternatives. However, tumors present a widespread heterogeneity, and many challenges remain to fully comprehend the influencing factors. Of particular importance is the Latin America population which i) is commonly underrepresented in clinical trials and large-scale epidemiological studies, ii) presents higher incidence and mortality rates in comparison to the developed world, and iii) is constituted by a genetically admixed population. Our research attempts to close this gap by investigating the interplay between sociodemographic, clinical, and lifestyle factors, and the effect these exert on the mutational profiles of Latin-American NSCLC patients. Methodology: The study population is derived from the NIRVANA study, a cross-sectional multicenter observational study aiming to characterize and validate molecular diagnostic technologies for NSCLC patients in Chile, Brazil, and Peru. Between July 2015 to October 2018, 5030 NSCLC patients were recruited from 37 centers, meeting inclusion criteria of age ≥18, histologically or cytological proven NSCLC diagnostic, and naïve treatment. Exclusion criteria included prior chemotherapy treatment and refusal to give informed consent. Primary or metastatic NSCLC samples were collected during standard of care biopsy and processed for the DNA and RNA isolation. Next Generation Sequencing (NSG) genomics profiles were obtained using the Oncomine Focus Assay (OFA). Covariates of interest, including sociodemographic, clinical, and lifestyle factors, were assessed at enrollment. QC-approved genomic profiles were obtained for 1864 participants. Results and Conclusions: The prevalence of mutations and fusions in the eight most relevant NSCLC genes (EGFR, KRAS, ALK, MET, RET, BRAF, ROS1 and ERBB2) varies based on sociodemographic, clinical and lifestyle characteristics. Clear distinctions emerged in the prevalence of EGFR, KRAS and ERBB2 mutations among the three countries (EGFR: 20.9%, 17.6%, 35.3%; KRAS: 21.8%, 15.6%, 10.3%; ERBB2: 2.8%, 3.3%, 4.4% for Brazil, Chile, and Peru, respectively). Furthermore, distinct association patterns were identified between the prevalence of genetic alterations and the studied factors, with attributes such as sex, tobacco use and ethnicity mostly influencing the occurrence of EGFR, ALK and ROS1 alterations. These findings provide novel insights into NSCLC studies among Latin-American patients, potentially serving as guidelines for more tailored strategies in the overall management of this underrepresented population. Citation Format: Javiera Garrido, Evelin González, Gonzalo Sepúlveda-Hermosilla, Matias Freire, Alejandro Blanco, Solange Rivas, Katherine Marcelain, Gareth I. Owen, Carolina Ibañez, Alejandro Corvalan, Marcelo Garrido, Rodrigo Assar, Rodrigo Lizana, Javier Cáceres-Molina, Diego Ampuero, Liliana Ramos, Paola Pérez, Osvaldo Aren, Sara Chernilo, Cristina Fernández, María Loreto Spencer, Jacqueline Flores, Giuliano Bernal, Mónica Ahumada, Germán Rasse, Carolina Sánchez, Maria Galli de Amorim, Gabriela Branco, Diana Noronha Nunes, Emmanuel Dias-Neto, Helano C. Freitas, NIRVANA team, Ricardo Armisén. Tumor genomic heterogeneity in non-small cell lung cancer (NSCLC) patients from Latin America [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6158.