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

IF 7.6 1区 医学 Q1 ONCOLOGY European Journal of Cancer Pub Date : 2025-02-22 DOI:10.1016/j.ejca.2025.115308
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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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.
Registered clinical trials: STARTRK-NG: NCT02650401; TAPISTRY: NCT04589845; STARTRK-2: NCT02568267
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来源期刊
European Journal of Cancer
European Journal of Cancer 医学-肿瘤学
CiteScore
11.50
自引率
4.80%
发文量
953
审稿时长
23 days
期刊介绍: The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.
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