Real-world experience with selumetinib in children with neurofibromatosis type 1: a multicentric retrospective study.

IF 3.1 2区医学 Q2 CLINICAL NEUROLOGY

Journal of Neuro-Oncology Pub Date : 2025-12-01 Epub Date: 2025-08-13 DOI:10.1007/s11060-025-05197-5

Claudia Santoro, Mariachiara Servedio, Maria Cristina Diana, Irene Russo, Elena Arkhangelskaya, Gianluca Piccolo, Andrea Santangelo, Angela Mastronuzzi, Antonella Cacchione, May El Hachem, Carmela Russo, Mario Cirillo, Ilaria Cecconi, Antonio Grasso, Mariateresa Loiotine, Nicola Santoro, Mariachiara Resta, Carmela De Meco, Consolata Soddu, Eugenia Spreafico, Bartolomeo Rossi, Chiara Fossati, Chiara Leoni, Silverio Perrotta, Teresa Perillo

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引用次数: 0

Abstract

Purpose: Selumetinib is a MEK inhibitor indicated for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibromas (PNs).

Methods: This retrospective study collected data from 70 patients (aged 3 - 18 years) with NF1 and symptomatic inoperable PNs treated with selumetinib as part of compassionate use at 11 Italian centers between October 2018 and October 2024. Assessments included the clinical benefit rate (CBR) after 24 months and at the last observation. Major response (MR) was defined as a ≥ 50% reduction from baseline in tumor volume. Adverse events (AEs), patient-reported pain and quality of life (QoL), and Eastern Cooperative Oncology Group performance status (ECOG PS), were also evaluated.

Results: Of 45/70 patients with available natural history data at C0, 33/45 (73.3%) had progressive disease (PD). Radiological evaluation at C6 in 17/33 patients showed 16 (94.1%) had stable disease (SD) or partial response (PR). 52/58 patients (91.5%) had SD or PR/MR at C12; final response at last radiological follow-up was PD (7.7%), SD (42.3%), PR (30.8%) and MR (19.2%). CBR was 83.3% (24/70) at C24 and 91.5% (43/47) at last radiological follow-up. Selumetinib significantly reduced pain perception and improved QoL and ECOG PS. The type of response at C6 seems to predict response at C12 and at last observation. Adverse events were generally mild (78% grade ≤ 2).

Conclusion: Our findings suggest that the response after 6 and 12 selumetinib cycles may predict long-term outcomes, providing clinicians with an early indicator for therapeutic decision-making.

Trial registration number: Not applicable.

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selumetinib治疗1型神经纤维瘤病儿童的实际经验：一项多中心回顾性研究

目的：Selumetinib是一种MEK抑制剂，适用于1型神经纤维瘤病（NF1）和症状性不能手术的丛状神经纤维瘤（PNs）患儿。方法：本回顾性研究收集了2018年10月至2024年10月在意大利11个中心接受selumetinib治疗的70例NF1和症状性无法手术的PNs患者（3 - 18岁）的数据。评估包括24个月后和最后一次观察时的临床获益率（CBR）。主要缓解（MR）定义为肿瘤体积比基线减少≥50%。不良事件（ae），患者报告的疼痛和生活质量（QoL），以及东部肿瘤合作组的表现状态（ECOG PS）也进行了评估。结果：在45/70的C0自然史资料中，33/45（73.3%）为进展性疾病（PD）。33例患者中有17例C6的放射学评估显示16例（94.1%）病情稳定（SD）或部分缓解（PR）。52/58例（91.5%）患者在C12时出现SD或PR/MR；最后放射随访的最终缓解为PD（7.7%）、SD（42.3%）、PR（30.8%）和MR（19.2%）。CBR在C24时为83.3%(24/70)，最后放射随访时为91.5%（43/47）。Selumetinib显著降低了疼痛感觉，改善了QoL和ECOG PS。C6时的反应类型似乎可以预测C12和最后观察时的反应。不良事件一般较轻（78%≤2级）。结论：我们的研究结果表明，6和12个selumetinib周期后的反应可以预测长期结果，为临床医生提供治疗决策的早期指标。试验注册号：不适用。

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来源期刊

Journal of Neuro-Oncology 医学-临床神经学

CiteScore

6.60

自引率

7.70%

发文量

277

审稿时长

3.3 months

期刊介绍： The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.