司美替尼治疗1型神经纤维瘤病儿童的真实世界经验：一项多中心回顾性研究。

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

作者信息

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

机构信息

Department of Women's and Children's Health and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

Division of Pediatric Oncology and Haematology "Policlinico di Bari", Bari, Italy.

出版信息

J Neurooncol. 2025 Aug 13. doi: 10.1007/s11060-025-05197-5.

DOI:10.1007/s11060-025-05197-5

PMID:40802118

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.

摘要

目的

司美替尼是一种MEK抑制剂，适用于1型神经纤维瘤病（NF1）且有症状的无法手术的丛状神经纤维瘤（PN）的儿科患者。

方法

这项回顾性研究收集了2018年10月至2024年10月期间在意大利11个中心作为同情用药接受司美替尼治疗的70例年龄在3至18岁之间的NF1且有症状的无法手术的PN患者的数据。评估包括24个月时和最后一次观察时的临床获益率（CBR）。主要缓解（MR）定义为肿瘤体积较基线缩小≥50%。还评估了不良事件（AE）、患者报告的疼痛和生活质量（QoL）以及东部肿瘤协作组体能状态（ECOG PS）。

结果

在C0时有45/70例患者有可用的自然病史数据，其中33/45（73.3%）有疾病进展（PD）。17/33例患者在C6时的影像学评估显示16例（94.1%）有疾病稳定（SD）或部分缓解（PR）。52/58例患者（91.5%）在C12时有SD或PR/MR；最后一次影像学随访时的最终缓解情况为PD（7.7%）、SD（42.3%）、PR（30.8%）和MR（19.2%）。CBR在C24时为83.3%（24/70），在最后一次影像学随访时为91.5%（43/47）。司美替尼显著降低了疼痛感知，改善了QoL和ECOG PS。C6时的缓解类型似乎可预测C12时和最后一次观察时的缓解情况。不良事件一般较轻（78%为≤2级）。