2026-04-14T03:14:55Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/130442025-10-24T10:41:43Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Mascarenhas, Leo author Albert, Catherine author Federman, Noah author DuBois, Steven author Bielack, Stefan author Orbach, Daniel author Gallego, Soledad author 2025-05-07T07:15:46Z 2025-05-07T07:15:46Z 2025-04-01 Pediatric patients; Sarcomas; Mesenchymal tumors Pacients pediàtrics; Sarcomes; Tumors mesenquimals Pacientes pediátricos; Sarcomas; Tumores mesenquimales Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma. This cohort included 91 patients (younger than 18 years) from two clinical trials: infantile fibrosarcoma (49), other soft tissue sarcomas or related mesenchymal tumors (41), and bone sarcoma (1). Treatment-related adverse events were of maximum grade 1 or 2 in 25% and 25% of patients, respectively. The overall response rate was 87% (95% CI, 78 to 93). In the wait-and-see analysis, 47 patients discontinued larotrectinib. Median time from discontinuation to disease progression was not reached. Sixteen patients had tumor progression during the wait-and-see period. All 16 patients resumed larotrectinib, and 15 (94%) achieved disease control, with 11 objective responses. Larotrectinib continues to demonstrate durable responses with favorable safety in children with TRK fusion sarcomas. Treatment discontinuation is feasible in select patients with objective response and clinical benefit noted in those who have disease progression after elective treatment discontinuation. Supported by Bayer Healthcare and Loxo Oncology, Inc, a wholly owned subsidiary of Eli Lilly and Company. S.G.D. was supported by Alex's Lemonade Stand Foundation. J.C. was supported by the Giant Pledge through the Royal Marsden Cancer Charity, and this work represents independent research supported by the National Institute for Health Research Biomedical Research Center at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. http://hdl.handle.net/11351/13044 Infants Proteïnes quinases - Inhibidors - Ús terapèutic Sarcoma - Tractament Càncer - Tractament 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 DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma Other subheadings::Other subheadings::Other subheadings::/drug therapy NAMED GROUPS::Persons::Age Groups::Child 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 ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::sarcoma Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::niño Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors