Clinicogenomic and treatment outcomes in RET fusion-positive NSCLC: A multicenter study in Latin American Hispanic patients

Arrieta O.; Cardona A.F.; Wagner-Gutiérrez N.; de Lima V.C.C.; Saldanha E.F.; Corrales L.; Freitas H.C.; Santana L.G.; Martín C.; Enrico D.; Motta R.; Zuluaga J.; Rojas L.; Ruiz-Patiño A.; Cruz G.; Valencia Á.; Viola L.; Mejía S.; Martínez S.; Carvajal C.; Sánchez N.; Gutierrez L.; de las Salas B.; Raez L.; Rolfo C. · Cancer Treatment and Research Communications (2025) · DOI: 10.1016/j.ctarc.2025.101004

Resumen

Background: 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. Methods: 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. Results: 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. Conclusions: 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.