2026-04-17T06:46:23Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/131202025-06-14T04:13:37Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Driemel, Christiane
author
Shen, Lin
author
Chung, Hyun Cheol
author
Cannon, Timothy
author
André, Thierry
author
GARRALDA, Elena
2025-06-14T04:13:36Z
2025-06-14T04:13:36Z
2025-05-22T08:32:24Z2025-05-22T08:32:24Z2025-05-02
http://hdl.handle.net/11351/13120
Colorectal cancer; Gastrointestinal cancer; TRK fusionCàncer colorectal; Càncer gastrointestinal; Fusió TRKCáncer colorrectal; Cáncer gastrointestinal; Fusión TRKBackground
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.
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
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
Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion