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Efficacy and safety of entrectinib in children with extracranial solid or central nervous system (CNS) tumours harbouring NTRK or ROS1 fusions

BACKGROUND: 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 tumo...

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Main Authors: Desai, Ami (Author) , Bagchi, Aditi (Author) , Armstrong, Amy E. (Author) , Tilburg, Cornelis M. van (Author) , Basu, Ellen M. (Author) , Robinson, Giles W. (Author) , Wang, Huanmin (Author) , Casanova, Michela (Author) , André, Nicolas (Author) , Campbell-Hewson, Quentin (Author) , Wu, Yeming (Author) , Cardenas, Alison (Author) , Ci, Bo (Author) , Ryklansky, Carolina (Author) , Devlin, Clare E. (Author) , Meneses-Lorente, Georgina (Author) , Wulff, Jade (Author) , Hutchinson, Katherine E. (Author) , Gajjar, Amar (Author) , Fox, Elizabeth (Author)
Format: Article (Journal)
Language:English
Published: 22 February 2025
In: European journal of cancer
Year: 2025, Volume: 220, Pages: 1-9
ISSN:1879-0852
DOI:10.1016/j.ejca.2025.115308
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ejca.2025.115308
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Author Notes:Ami V. Desai, Aditi Bagchi, Amy E. Armstrong, Cornelis M. van Tilburg, Ellen M. Basu, Giles W. Robinson, Huanmin Wang, Michela Casanova, Nicolas André, Quentin Campbell-Hewson, Yeming Wu, Alison Cardenas, Bo Ci, Carolina Ryklansky, Clare E. Devlin, Georgina Meneses-Lorente, Jade Wulff, Katherine E. Hutchinson, Amar Gajjar, Elizabeth Fox
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Summary:BACKGROUND: 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.
Item Description:Gesehen am 23.03.2026
Physical Description:Online Resource
ISSN:1879-0852
DOI:10.1016/j.ejca.2025.115308

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