2026-04-17T16:58:17Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/131202025-06-14T04:13:37Zcom_2072_378070com_2072_378040col_2072_378092

Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer Driemel, Christiane Shen, Lin Chung, Hyun Cheol Cannon, Timothy André, Thierry GARRALDA, Elena Aparell digestiu - Càncer - Tractament Proteïnes quinases - Inhibidors - Ús terapèutic Avaluació de resultats (Assistència sanitària) ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors Other subheadings::Other subheadings::/therapeutic use TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas Otros calificadores::Otros calificadores::/uso terapéutico Colorectal cancer; Gastrointestinal cancer; TRK fusion Càncer colorectal; Càncer gastrointestinal; Fusió TRK Cáncer colorrectal; Cáncer gastrointestinal; Fusión TRK Background Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer. Methods Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1. Results As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients with CRC, 16 (62 %) had known microsatellite instability-high (MSI-H) status. For the 43 IRC-eligible patients, overall response rate was 28 % (95 % confidence interval [CI] 15–44) for all patients and 44 % (95 % CI 24–65) for those with CRC. In patients overall and in those with CRC, median duration of response was 27 months (95 % CI 6–not estimable [NE]) and 27 months (95 % CI 6–NE), median progression-free survival was 6 months (95 % CI 5–9) and 7 months (95 % CI 6–NE), and median overall survival was 13 months (95 % CI 7–29) and 29 months (95 % CI 7–NE), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in seven (16 %) patients. There were no deaths due to TRAEs. Conclusion Larotrectinib demonstrated long durability, extended survival and manageable safety in patients with TRK fusion GI cancer, including those with MSI-H CRC. This supports the wider adoption of next-generation sequencing testing for NTRK gene fusions in patients with GI cancer. These studies were funded by Bayer Healthcare and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company. Dr Drilon was supported in part by the National Cancer Institute of the National Institutes of Health P30 CA008748, 1R01CA226864–01A1 and Nonna’s Garden. 2025-06-14T04:13:36Z 2025-06-14T04:13:36Z 2025-06-14T04:13:36Z 2025-05-22T08:32:24Z 2025-05-22T08:32:24Z 2025-05-02 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13120 European Journal of Cancer;220 https://doi.org/10.1016/j.ejca.2025.115338 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia