贝伐珠单抗联合伏立诺他治疗复发性世界卫生组织分级 4 级恶性脑胶质瘤的 II 期研究。
Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma.
机构信息
University of Florida, Gainesville, Florida, USA.
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
出版信息
Oncologist. 2018 Feb;23(2):157-e21. doi: 10.1634/theoncologist.2017-0501. Epub 2017 Nov 13.
LESSONS LEARNED
Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma.Treatment of recurrent glioblastoma remains challenging as this study and others attempt to improve progression-free survival and overall survival with BEV-containing regimens.
BACKGROUND
Recurrent glioblastoma (GBM; World Health Organization grade 4) continues to have a very poor prognosis. Bevacizumab (BEV) has been shown to improve progression-free survival (PFS) in recurrent GBM and is approved by the U.S. Food and Drug Administration for the treatment of recurrent GBM. Combination regimens have been explored, and in this phase II nonrandomized trial, we evaluated the efficacy of BEV combined with histone deacetylase inhibitor vorinostat (VOR) in recurrent GBM.
MATERIALS AND METHODS
In this phase II, single-center, nonrandomized study, subjects with recurrent GBM received BEV 10 mg/kg intravenously (IV) every 2 weeks combined with VOR 400 mg p.o. daily for 7 days on, 7 days off, in a 28-day cycle. The primary endpoint was 6-month PFS (PFS6).
RESULTS
Forty patients with recurrent GBM were enrolled and evaluated. PFS6 was 30.0% (95% confidence interval [CI] 16.8%-44.4%). Median overall survival (OS) was 10.4 months (95% CI 7.6-12.8 months). Overall radiographic response rate was 22.5% based on 9 partial responses. The most common grade 2 and above treatment-related adverse events were lymphopenia (55%), leukopenia (45%), neutropenia (35%), and hypertension (33%). Grade 4 adverse events were leukopenia (3%), neutropenia (3%), sinus bradycardia (3%), and venous thromboembolism (3%). Two deaths occurred in this study, with one due to tumor progression and another possibly related as death not otherwise specified.
CONCLUSION
Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy.
经验教训
贝伐单抗（BEV）和伏立诺他联合治疗复发性胶质母细胞瘤患者可耐受良好。复发性胶质母细胞瘤的治疗仍然具有挑战性，因为本研究和其他研究试图通过含 BEV 的方案来改善无进展生存期和总生存期。
背景
复发性胶质母细胞瘤（GBM；世界卫生组织分级 4）的预后仍然非常差。贝伐单抗（BEV）已被证明可改善复发性 GBM 的无进展生存期（PFS），并已被美国食品和药物管理局批准用于治疗复发性 GBM。联合方案已被探索，在这项 II 期非随机试验中，我们评估了 BEV 联合组蛋白去乙酰化酶抑制剂伏立诺他（VOR）在复发性 GBM 中的疗效。
材料和方法
在这项 II 期、单中心、非随机研究中，复发性 GBM 患者接受 BEV 10 mg/kg 静脉注射（IV），每 2 周 1 次，同时联合 VOR 400 mg 口服，每日 1 次，连用 7 天，停药 7 天，每 28 天为 1 个周期。主要终点为 6 个月无进展生存期（PFS6）。
结果
40 例复发性 GBM 患者入组并进行了评估。PFS6 为 30.0%（95%置信区间 [CI] 16.8%-44.4%）。中位总生存期（OS）为 10.4 个月（95% CI 7.6-12.8 个月）。根据 9 例部分缓解，总体放射学缓解率为 22.5%。最常见的 2 级及以上治疗相关不良事件为淋巴细胞减少症（55%）、白细胞减少症（45%）、中性粒细胞减少症（35%）和高血压（33%）。4 级不良事件为白细胞减少症（3%）、中性粒细胞减少症（3%）、窦性心动过缓（3%）和静脉血栓栓塞症（3%）。本研究中有 2 例死亡，1 例与肿瘤进展有关，另 1 例可能与未明确的死亡有关。
结论
BEV 和 VOR 的联合治疗可耐受良好。与 BEV 单药治疗相比，该联合治疗方案并未改善 PFS6 或中位 OS。
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