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Lookup NU author(s): Dr Quentin Campbell Hewson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The AuthorsBackground: Entrectinib, a central nervous system (CNS)-penetrant TRK/ROS1 inhibitor, has demonstrated clinical activity in children with NTRK1/2/3 or ROS1 fusion-positive extracranial solid and CNS tumours. We present integrated data of entrectinib in children with NTRK or ROS1 fusion-positive tumours from the STARTRK-NG, TAPISTRY, and STARTRK-2 trials. Methods: Efficacy analyses were undertaken on TRK/ROS1 inhibitor-naïve patients aged <18 years with metastatic/locally advanced NTRK1/2/3 or ROS1 fusion-positive extracranial solid or CNS tumours who received ≥1 entrectinib dose and had ≥6 months of follow-up from enrolment. Tumour responses were confirmed by blinded independent central review (BICR) per RECIST v1.1/RANO criteria. Primary endpoint: BICR-assessed confirmed objective response rate (cORR). Key secondary endpoints: duration of response (DoR); time to response (TtR); safety. Results: As of 16 July 2023, out of 91 safety-evaluable patients, 64 (NTRK: n=44; ROS1: n=20) were efficacy evaluable. In the NTRK and ROS1 subgroups, respectively, median age was 4.0 years and 7.5 years; median survival follow-up was 24.2 months and 27.6 months. cORR was 72.7 % (NTRK, 95 % confidence interval [CI]: 57.2–85.0) and 65.0 % (ROS1, 95 % CI: 40.8–84.6). Median DoR was not reached (NTRK, 95 % CI: 25.4–not evaluable [NE]); ROS1, 95 % CI: 16.2–NE); median TtR was 1.9 months in both subgroups. The most frequently reported treatment-related adverse events included weight gain (35.2 %) and anaemia (31.9 %). Conclusion: Integrated data from three trials confirm entrectinib induces rapid and durable responses in children with NTRK or ROS1 fusion-positive tumours. The increased duration of safety monitoring does not demonstrate new or cumulative toxicity. Registered clinical trials: STARTRK-NG: NCT02650401; TAPISTRY: NCT04589845; STARTRK-2: NCT02568267
Author(s): Desai AV, Bagchi A, Armstrong AE, van Tilburg CM, Basu EM, Robinson GW, Wang H, Casanova M, Andre N, Campbell-Hewson Q, Wu Y, Cardenas A, Ci B, Ryklansky C, Devlin CE, Meneses-Lorente G, Wulff J, Hutchinson KE, Gajjar A, Fox E
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Year: 2025
Volume: 220
Print publication date: 02/05/2025
Online publication date: 22/02/2025
Acceptance date: 11/02/2025
Date deposited: 08/04/2025
ISSN (print): 0959-8049
ISSN (electronic): 1879-0852
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.ejca.2025.115308
DOI: 10.1016/j.ejca.2025.115308
Data Access Statement: For eligible studies, qualified researchers may request access to individual patient-level clinical data through a data request platform. At the time of writing, this request platform is Vivli https://vivli.org/ourmember/roche/. For up-to-date details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: https://go.roche.com/data_sharing. Anonymized records for individual patients across more than one data source external to Roche cannot, and should not, be linked because of a potential increase in the risk of patient re-identification.
PubMed id: 40086048
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