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
{"title":"Efficacy and safety of entrectinib in children with extracranial solid or central nervous system (CNS) tumours harbouring NTRK or ROS1 fusions","authors":"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","doi":"10.1016/j.ejca.2025.115308","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Entrectinib, a central nervous system (CNS)-penetrant TRK/ROS1 inhibitor, has demonstrated clinical activity in children with <em>NTRK1/2/3</em> or <em>ROS1</em> fusion-positive extracranial solid and CNS tumours. We present integrated data of entrectinib in children with <em>NTRK</em> or <em>ROS1</em> fusion-positive tumours from the STARTRK-NG, TAPISTRY, and STARTRK-2 trials.</div></div><div><h3>Methods</h3><div>Efficacy analyses were undertaken on TRK/ROS1 inhibitor-naïve patients aged <18 years with metastatic/locally advanced <em>NTRK1/2/3</em> or <em>ROS1</em> 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.</div></div><div><h3>Results</h3><div>As of 16 July 2023, out of 91 safety-evaluable patients, 64 (<em>NTRK</em>: n=44; <em>ROS1</em>: n=20) were efficacy evaluable. In the <em>NTRK</em> and <em>ROS1</em> 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 % (<em>NTRK,</em> 95 % confidence interval [CI]: 57.2–85.0) and 65.0 % (<em>ROS1</em>, 95 % CI: 40.8–84.6). Median DoR was not reached (<em>NTRK,</em> 95 % CI: 25.4–not evaluable [NE]); <em>ROS1</em>, 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 %).</div></div><div><h3>Conclusion</h3><div>Integrated data from three trials confirm entrectinib induces rapid and durable responses in children with <em>NTRK</em> or <em>ROS1</em> fusion-positive tumours. The increased duration of safety monitoring does not demonstrate new or cumulative toxicity.</div><div><strong>Registered clinical trials:</strong> STARTRK-NG: NCT02650401; TAPISTRY: NCT04589845; STARTRK-2: NCT02568267</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"220 ","pages":"Article 115308"},"PeriodicalIF":7.6000,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804925000899","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
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