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Clinical Trial
. 2018 Feb;23(2):157-e21.
doi: 10.1634/theoncologist.2017-0501. Epub 2017 Nov 13.

Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma

Ashley Ghiaseddin  1 , David Reardon  2 , Woody Massey  3 , Alex Mannerino  3 , Eric S Lipp  3 , James E Herndon 2nd  3 , Frances McSherry  3 , Annick Desjardins  3 , Dina Randazzo  3 , Henry S Friedman  3 , Katherine B Peters  4
Affiliations
Clinical Trial

Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma

Ashley Ghiaseddin et al. Oncologist. 2018 Feb.

Abstract
in English, Chinese

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.

经验总结

• 贝伐珠单抗（BEV）和伏立诺他联合给药方案治疗胶质母细胞瘤复发患者的耐受性良好。

• 复发性胶质母细胞瘤的治疗仍然充满挑战, 本研究和其他研究试图改善含BEV给药方案的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4级）的预后仍然很差。贝伐珠单抗（BEV）已被证实可以改善复发性GBM的无进展生存率（PFS）, 并且已获美国食品药品监督管理局批准用于治疗复发性GBM。联合给药方案已经进行探索。在本项II期非随机化试验中, 我们评价了BEV与组蛋白脱乙酰酶抑制剂伏立诺他（VOR）联合给药治疗复发性GBM的疗效。

材料与方法.在本项II期、单中心、非随机化研究中, 复发性GBM患者每两周通过静脉注射（IV）接受BEV 10 mg/kg, 同时每天口服VOR 400 mg, 共7天, 然后停药7天, 28天为一个给药周期。研究的主要终点为6个月PFS（PFS6）。

结果.40例复发性GBM患者入组研究并参与了评价。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）。9例患者达到部分缓解, 总体影像学缓解率为22.5%。最常见的≥2级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（3%）。研究期间发生了2例死亡, 1例死于肿瘤进展, 另1例死亡可能与治疗有关（死亡原因未说明）。

结论.BEV和VOR联合给药可良好耐受。与BEV单药疗法相比, BEV和VOR联合给药并未改善本研究人群的PFS6或中位OS。

Trial registration: ClinicalTrials.gov NCT01738646.

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