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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enterrectinib治疗含有NTRK或ROS1融合的儿童颅外实体或中枢神经系统（CNS）肿瘤的疗效和安全性

enterrectinib是一种中枢神经系统（CNS）渗透性TRK/ROS1抑制剂，在NTRK1/2/3或ROS1融合阳性的颅外实体瘤和CNS肿瘤患儿中显示出临床活性。我们提供了来自STARTRK-NG、tapisty和STARTRK-2试验的enterrecinib在NTRK或ROS1融合阳性肿瘤儿童中的综合数据。方法对18岁的TRK/ROS1 inhibitor-naïve转移性/局部晚期NTRK1/2/3或ROS1融合阳性颅外实体瘤或中枢神经系统肿瘤患者进行疗效分析，这些患者接受≥1剂量的enterrectinib治疗，自入组以来随访≥6个月。根据RECIST v1.1/RANO标准，通过盲法独立中心评价（BICR）确认肿瘤反应。主要终点：bicr评估的确认客观缓解率（cORR）。关键次要终点：反应持续时间（DoR）；反应时间（TtR）；安全。结果截至2023年7月16日，在91例可安全评估的患者中，64例(NTRK: n=44；ROS1: n=20)均可评价疗效。NTRK和ROS1亚组的中位年龄分别为4.0岁和7.5岁；中位生存期分别为24.2个月和27.6个月。cORR分别为72.7 % （NTRK， 95 %可信区间[CI]: 57.2-85.0）和65.0 % （ROS1, 95 % CI: 40.8-84.6）。未达到中位DoR (NTRK, 95 % CI: 25.4，不可评价[NE])；Ros1, 95 % ci: 16.2-ne)；两个亚组的中位TtR均为1.9个月。最常见的治疗相关不良事件包括体重增加（35.2% %）和贫血（31.9% %）。结论：三项试验的综合数据证实，恩替尼对NTRK或ROS1融合阳性肿瘤患儿可产生快速、持久的反应。安全监测持续时间的增加并未显示出新的或累积的毒性。注册临床试验：STARTRK-NG: NCT02650401；TAPISTRY: NCT04589845;STARTRK-2: NCT02568267

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来源期刊

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.