Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2015 Jun 15;21(12):2666-70. doi: 10.1158/1078-0432.CCR-14-3119. Epub 2015 Mar 23.
On July 3, 2014, the FDA granted accelerated approval for belinostat (Beleodaq; Spectrum Pharmaceuticals, Inc.), a histone deacetylase inhibitor, for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). A single-arm, open-label, multicenter, international trial in the indicated patient population was submitted in support of the application. Belinostat was administered intravenously at a dose of 1000 mg/m(2) over 30 minutes once daily on days 1 to 5 of a 21-day cycle. The primary efficacy endpoint was overall response rate (ORR) based on central radiology readings by an independent review committee. The ORR was 25.8% [95% confidence interval (CI), 18.3-34.6] in 120 patients that had confirmed diagnoses of PTCL by the Central Pathology Review Group. The complete and partial response rates were 10.8% (95% CI, 5.9-17.8) and 15.0% (95% CI, 9.1-22.7), respectively. The median duration of response, the key secondary efficacy endpoint, was 8.4 months (95% CI, 4.5-29.4). The most common adverse reactions (>25%) were nausea, fatigue, pyrexia, anemia, and vomiting. Grade 3/4 toxicities (≥5.0%) included anemia, thrombocytopenia, dyspnea, neutropenia, fatigue, and pneumonia. Belinostat is the third drug to receive accelerated approval for the treatment of relapsed or refractory PTCL.
2014 年 7 月 3 日，美国食品药品监督管理局（FDA）批准了贝林司他（Beleodaq；Spectrum Pharmaceuticals，Inc.）用于治疗复发或难治性外周 T 细胞淋巴瘤（PTCL）患者。一项在该适应证患者人群中开展的、单臂、开放标签、多中心、国际性试验被提交用于支持该适应证申请。贝林司他以 1000mg/m2 的剂量静脉输注，输注时间 30 分钟，每日 1 次，连续用药 5 天，每 21 天为 1 个周期。主要疗效终点为独立评审委员会根据中心放射学评估的总缓解率（ORR）。在经中央病理审查组确认为 PTCL 的 120 例患者中，ORR 为 25.8%（95%CI，18.3-34.6）。完全缓解率和部分缓解率分别为 10.8%（95%CI，5.9-17.8）和 15.0%（95%CI，9.1-22.7）。关键次要疗效终点缓解持续时间的中位数为 8.4 个月（95%CI，4.5-29.4）。最常见的不良反应（>25%）为恶心、疲乏、发热、贫血和呕吐。3/4 级毒性（≥5.0%）包括贫血、血小板减少、呼吸困难、中性粒细胞减少、疲乏和肺炎。贝林司他是第 3 个获加速批准用于治疗复发或难治性 PTCL 的药物。
