Purpose

NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory.

Methods

The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL).

Results

Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores.

Conclusions

Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).

中文翻译：

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成像作为早期生物标志物，预测进展性 NF2 相关前庭神经鞘瘤对依维莫司的敏感性

目的

NF2相关神经鞘瘤病 (NF2) 的特点是双侧前庭神经鞘瘤 (VS)，通常导致听力和神经功能缺陷，目前尚无 FDA 批准的药物治疗。临床前研究强调了 mTORC1 抑制在延缓神经鞘瘤进展方面的潜力。我们对依维莫司治疗 NF2 患者进行性 VS 进行了一项前瞻性开放标签 II 期研究，并研究了影像学作为预测生长轨迹影响的潜在生物标志物。

方法

该试验招募了 12 名患有进行性 VS 的 NF2 患者。参与者每天接受口服依维莫司治疗，持续 52 周。每季度进行一次脑成像。作为主要终点，放射学反应 (RR) 定义为 目标 V​​S 体积减少≥ 20%。次要终点包括其他肿瘤的 RR、听力结果、药物安全性和生活质量 (QOL)。

结果

八名参与者完成了试验，四名参与者由于明显的体积 VS 进展而提前停药。治疗 52 周后，中位年 VS 增长​​率从基线时的 77.2% 降至 29.4%。没有 VS RR，8 名参与者中有 3 名 (37.5%) 病情稳定。治疗 3 个月后 VS 体积减少或不变可预测 12 个月时稳定。八名参与者中的七名在治疗期间听力稳定，除了一名单词识别得分下降之外。十二名参与者中有十名报告说他们的生活质量分数仅发生了微小的变化。

结论

3 个月时的体积成像可以作为早期生物标志物来预测对依维莫司治疗的长期敏感性。依维莫司可能是一种安全的治疗选择，可减少听力和神经系统状况稳定的患者 NF2 相关 VS 的生长。 TRN：NCT01345136（2011 年 4 月 29 日）。