Pediatric Oncology Branch, Center for Cancer research, National Cancer Institute, Bethesda, Maryland, USA.
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Neuro Oncol. 2022 Nov 2;24(11):1978-1988. doi: 10.1093/neuonc/noac109.
Selumetinib was recently approved for the treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). This parallel phase II study determined the response rate to selumetinib in children with NF1 PN without clinically significant morbidity.
Children with NF1 and inoperable PNs, which were not yet causing clinically significant morbidity but had the potential to cause symptoms, received selumetinib at 25 mg/m2 orally twice daily (1 cycle = 28 days). Volumetric magnetic resonance imaging analysis and outcome assessments, including patient-reported (PRO), observer-reported, and functional outcome measures were performed every 4 cycles for 2 years, with changes assessed over time. A confirmed partial response (cPR) was defined as PN volume decrease of ≥20% on at least 2 consecutive scans ≥3 months apart.
72% of subjects experienced a cPR on selumetinib. Participants received selumetinib for a median of 41 cycles (min 2, max 67) at data cutoff. Approximately half of the children rated having some target tumor pain at baseline, which significantly decreased by pre-cycle 13. Most objectively measured baseline functions, including visual, motor, bowel/bladder, or airway function were within normal limits and did not clinically or statistically worsen during treatment.
Selumetinib resulted in PN shrinkage in most subjects with NF1 PN without clinically significant morbidity. No new PN-related symptoms developed while on selumetinib, and PRO measures indicated declines in tumor-related pain intensity. This supports that selumetinib treatment may prevent the development of PN-related morbidities, though future prospective studies are needed to confirm these results.
ClinicalTrials.gov NCT01362803.
塞来替尼最近被批准用于治疗 1 型神经纤维瘤病（NF1）儿童无法手术的症状性丛状神经纤维瘤（PN）。这项平行的 2 期研究确定了塞来替尼在 NF1 PN 儿童中的反应率，这些儿童没有明显的发病率，但有可能出现症状。
患有 NF1 和无法手术的 PN 的儿童，这些 PN 尚未导致明显的发病率，但有可能导致症状，每天口服 25mg/m2 塞来替尼两次（1 个周期=28 天）。在 2 年内每 4 个周期进行一次容积磁共振成像分析和结果评估，包括患者报告（PRO）、观察者报告和功能结果测量，随着时间的推移评估变化。确认的部分缓解（cPR）定义为至少连续两次扫描至少相隔 3 个月，PN 体积减少≥20%。
72%的受试者在塞来替尼治疗后出现 cPR。数据截止时，参与者接受塞来替尼治疗的中位数为 41 个周期（最小 2，最大 67）。大约一半的儿童在基线时有一些目标肿瘤疼痛，在第 13 个周期前明显减轻。大多数基线的客观测量功能，包括视觉、运动、肠/膀胱或气道功能均在正常范围内，在治疗过程中没有临床或统计学上的恶化。
塞来替尼使大多数 NF1 PN 无明显发病率的儿童的 PN 缩小。在服用塞来替尼期间，没有新的与 PN 相关的症状出现，PRO 测量表明肿瘤相关疼痛强度下降。这支持塞来替尼治疗可能预防 PN 相关发病率的发展，尽管需要未来的前瞻性研究来证实这些结果。
ClinicalTrials.gov NCT01362803。
