Clinicogenomic and treatment outcomes in RET fusion-positive NSCLC: A multicenter study in Latin American Hispanic patients
Year: 2025
Type: article
Study design: Observational Study
Abstract: • RET+ NSCLC in Latin America: CT+ICI 43.5% ORR; targeted therapy longer PFS • RET-selective inhibitors showed longest OS in RET+ NSCLC, supporting first-line • RET fusions detected by NGS in Latin American NSCLC, KIF5B most frequent partner • Brain metastases associated with shorter OS in RET+ NSCLC patients in Latin America • First Latin American RET+ NSCLC cohort: targeted therapy superior outcomes RET fusions represent a rare but actionable molecular subtype in non-small cell lung cancer (NSCLC), comprising approximately 1% of cases. Despite the availability of selective RET inhibitors (RETsi), data on Hispanic populations, particularly from Latin America, remain limited. This retrospective multicenter study evaluated clinical, genomic, and treatment-related outcomes in patients with advanced RET fusion-positive NSCLC across five Latin American countries. Molecular profiling was conducted using DNA/RNA sequencing and FISH, and treatment regimens were classified by line of therapy and drug class, including chemotherapy, immunotherapy, multikinase inhibitors, and RETsi. Among 51 patients treated between January 2016 and April 2023, the majority were never or former smokers with adenocarcinoma histology. KIF5B was the predominant RET fusion partner. Co-occurring mutations included TP53 and CDKN2A/B. First-line therapy most commonly involved chemotherapy with or without immunotherapy. Although RETsi use was limited in early lines, patients receiving targeted therapy had improved progression-free survival in the second-line setting. Overall survival outcomes were consistent with prior global reports. This Latin American cohort of RET fusion-positive NSCLC patients exhibited consistent molecular features and treatment responses. Expanded access to RET-selective therapies is needed to optimize outcomes in this population.
Authors: Oscar Arrieta, Andrés F. Cardona, Nicolle Wagner-Gutiérrez, Vladmir Cláudio Cordeiro de Lima, Erick Figueiredo Saldanha, Luis Corrales, Helano Carioca Freitas, Leonardo Gil Santana, Claudio Martín, Diego Enrico, Rodrigo Motta, Jairo Zuluaga, Leonardo Rojas, Alejandro Ruiz-Patiño, Graciela Cruz, Ángel Valencia, Lucia Viola, Sergio Mejía, Stella Martínez, Carlos Carvajal, Natalia Sánchez, Liliana Gutierrez, Briegel de las Salas, Luis Raez, Christian Rolfo
Institutions: Instituto Nacional de Cancerología, Universidad El Bosque, Centro de Tratamiento e investigación sobre cáncer Luis Carlos Sarmiento Angulo, Universidad de Los Andes, AC Camargo Hospital, Instituto Alexander Fleming, Foundation for Clinical and Applied Cancer Research, Fundación Neumológica Colombiana, Memorial Healthcare System, Mount Sinai Health System, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,740
OpenAlex ID: W4414417614