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. 2025 Sep 18:45:101004.
doi: 10.1016/j.ctarc.2025.101004. Online ahead of print.

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

Oscar Arrieta  1 , Andrés F Cardona  2 , Nicolle Wagner-Gutiérrez  3 , Vladmir Cláudio Cordeiro de Lima  4 , Erick Figueiredo Saldanha  4 , Luis Corrales  5 , Helano Carioca Freitas  4 , Leonardo Gil Santana  4 , Claudio Martín  6 , Diego Enrico  6 , Rodrigo Motta  7 , Jairo Zuluaga  8 , Leonardo Rojas  8 , Alejandro Ruiz-Patiño  9 , Graciela Cruz  1 , Ángel Valencia  1 , Lucia Viola  10 , Sergio Mejía  11 , Stella Martínez  8 , Carlos Carvajal  8 , Natalia Sánchez  12 , Liliana Gutierrez  12 , Briegel de Las Salas  12 , Luis Raez  13 , Christian Rolfo  14 ; on behalf CLICaP
Affiliations
Free article

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

Oscar Arrieta et al. Cancer Treat Res Commun. .
Free article

Abstract

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.

Keywords: Gene rearrangement; Genomic; Molecular biology; Non-small cell lung cancer; RET; Targeted therapy.

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Conflict of interest statement

Declaration of competing interest Andrés F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Foundation Medicine, Roche Diagnostics, Thermo Fisher, Broad Institute, Amgen, Flatiron Health, Teva Pharma, Rochem Biocare, Bayer, INQBox, and The Foundation for Clinical and Applied Cancer Research – FICMAC. Additionally, he was linked and received honoraria as an advisor and participated in a speakers' bureau. He provided expert testimony to EISAI, Merck Serono, Janssen Pharmaceutical, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, Guardant Health, Illumina, and the Foundation for Clinical and Applied Cancer Research (FICMAC). Oscar Arrieta reports personal fees from Pfizer, grants and individual fees from AstraZeneca, grants and individual fees from Boehringer-Ingelheim, Lilly, Merck, Bristol Myers Squibb, and Roche, outside the submitted work. Christian Rolfo reports a relation with Mylan, Archer Biosciences, Oncopass, Inivata, Merck Serono, Novartis, MSD, Boehringer Ingelheim, Guardant Health, etc., AstraZeneca as part of the Speakers' Bureau. Also, he received research funding from Pfizer and had uncompensated Relationships with OncoDNA, Biomark, and Guardant Health. Leonardo Rojas received honoraria as an advisor and participated in the speakers’ bureau for Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, AstraZeneca, and Eli Lilly. Additionally, he was linked and received honoraria as a researcher. The other authors declare no conflicts of interest.

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