A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma
A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma
复制标题
DOI：
10.1007/s11060-016-2172-3
复制
发表时间：
2016-09-01
影响因子：
3.9
通讯作者：
Hainsworth, John D.
中科院分区：
文献类型：
--
作者：
Shih, Kent C.;Chowdhary, Sajeel;Hainsworth, John D.
标准治疗后进展的脑膜瘤具有挑战性，有效的化疗选择有限。这项II期试验评估了依维莫司联合贝伐单抗治疗复发性、进展性脑膜瘤患者的疗效，这些患者接受了手术切除和适当的局部放疗。手术切除和放疗标准治疗后复发性脑膜瘤（WHO I、II或III级）患者接受贝伐单抗（10 mg/kg IV，第1天和第15天）和依维莫司（10 mg PO，每日一次），每28天为一周期。每2个周期评价一次缓解。主要终点为无进展生存期（PFS）。次要终点包括缓解率、总生存期和安全性。17例中位年龄为59岁（29-84岁）的患者接受了研究治疗。研究入组时的WHO分级包括：I，5（29%）; II，7（41%）; III，4（24%）;未知，1（6%）。患者接受中位8个周期（1-37）;所有患者均停止研究治疗。在15名患者（88%）中观察到SD的最佳反应，6名患者的SD> 12个月。总体中位PFS为22个月（95% CI 4.5-26.8），WHO II级和III级肿瘤患者的PFS大于I级肿瘤患者（22.0个月vs 17.5个月）。4例患者因毒性而停止治疗（蛋白尿，2例;结肠炎，1例;血小板减少症，1例）。然而，其他3级毒性并不常见，没有患者出现4级毒性。依维莫司和贝伐单抗的组合耐受性良好，并且在88%的患者中产生稳定的疾病;疾病稳定的中位持续时间为10个月（2-29）。这项前瞻性试验的中位PFS与贝伐单抗治疗复发性脑膜瘤的既往回顾性报告相似。
Meningiomas that progress after standard therapies are challenging with limited effective chemotherapy options. This phase II trial evaluated the efficacy of everolimus plus bevacizumab in patients with recurrent, progressive meningioma after treatment with surgical resection and local radiotherapy when appropriate. Patients with recurrent meningioma (WHO grade I, II, or III) following standard treatments with surgical resection and radiotherapy received bevacizumab (10 mg/kg IV days 1 and 15) and everolimus (10 mg PO daily) each 28 day cycle. Evaluation of response occurred every 2 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, overall survival and safety. Seventeen patients with a median age of 59 years (29-84) received study treatment. WHO grades at study entry included: I, 5 (29 %); II, 7 (41 %); III, 4 (24 %); unknown, 1 (6 %). Patients received a median of 8 cycles (1-37); all patients are off study treatment. A best response of SD was observed in 15 patients (88 %), and 6 patients had SD for > 12 months. Overall median PFS was 22 months (95 % CI 4.5-26.8) and was greater for patients with WHO grade II and III compared to grade I tumors (22.0 months vs 17.5 months). Four patients discontinued treatment due to toxicity (proteinuria, 2; colitis, 1, thrombocytopenia, 1). However, other grade 3 toxicity was uncommon, and no patient had grade 4 toxicity. The combination of everolimus and bevacizumab was well-tolerated, and produced stable disease in 88 % of patients; the median duration of disease stabilization of 10 months (2-29). The median PFS from this prospective trial was similar to previous retrospective reports of bevacizumab in the treatment of recurrent meningioma.