背景：GOG-0218 建立了晚期卵巢癌标准一线化疗每 3 周（q3w）加入 BEV 15mg/kg，持续 15 个月，但最佳 BEV 持续时间仍不清楚。我们报告了一项旨在解决这个问题的随机 3 期临床试验的初步结果。

Background: GOG-0218 established the addition of BEV 15 mg/kg every 3 weeks (q3w) for 15 months to standard front-line chemotherapy for advanced ovarian cancer, but the optimal BEV duration remained unknown. We report primary results from a randomized phase 3 trial designed to address this question.

方法：符合条件的 FIGO IIB-IV 期 EOC、FTC 或 PPC 和 ECOG PS#2 患者接受一期细胞减灭术，然后接受 6个周期的化疗（紫杉醇175mg/m2+卡铂 AUC 5Q3W）和 BEV（15mg/kg q3w）。患者随机接受 BEV 治疗 15个月（标准组 BEV15）或 30 个月（实验组 BEV30），按 FIGO 分期/残留肿瘤（IIB-IIIC 期/无残留肿瘤与 IIB-IIIC期/残留肿瘤或 IV 期）分层。主要终点研究者根据 recistv1.1 评估无进展生存率（PFS）。次要终点是总生存率（OS）、客观有效率、生活质量、安全性和耐受性。该试验设计了 80.2%的功率来检测有利于 BEV30（双侧对数秩）的危险比（HR）为 0.66，5%显著性水平，10%退出率）后 697 PFS 事件。这项试验是由 F。Hoffmann La Roche 有限公司，根据 ENGOT 模型 A 执行。

Methods: Eligible pts with FIGO stage IIB–IV EOC, FTC, or PPC and ECOG PS ≤2 underwent primary cytoreductive surgery followed by 6 cycles of chemotherapy (paclitaxel 175 mg/m2 + carboplatin AUC 5 q3w) and BEV (15 mg/kg q3w). Pts were randomized to receive BEV for either 15 months (standard arm BEV15) or 30 months (experimental arm BEV30), stratified by FIGO stage/residual tumor (stage IIB–IIIC/no residual tumor vs stage IIB–IIIC/residual tumor or stage IV). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST v1.1. Secondary endpoints were overall survival (OS), objective response rate, quality of life, safety, and tolerability. The trial was designed with 80.2% power to detect a hazard ratio (HR) of 0.66 favoring BEV30 (2-sided log-rank test, 5% significance level, 10% dropout rate) after 697 PFS events. The trial was funded by F. Hoffmann-La Roche Ltd., performed according to ENGOT model A.

结果：从 2011 年 11 月到 2013 年 8 月，来自 161 个中心的 927 名女性（83%患有 EOC）被随机分组。基线特征在两组之间保持平衡；中位年龄 61 岁，96%有 Ecog/Ps:0/1，58%无肿瘤残留，77%有高级别浆膜组织学。两组（BEV15 Vs BEV30）严重的不良事件分别为 51/448 例患者（11%）与 61/442 例患者（14%）：高血压（2.7%/4.5%）、血栓栓塞事件（2.2%/3.2%）、瘘（3.1%/1.1%）、胃肠道穿孔（0.2%/0.9%）、蛋白尿（0.7%/1.4%）、出血（0.2%/0.9%）和心肌梗死（0%/1.1%）。疗效见下表。

Results: From Nov 2011 to Aug 2013, 927 women (83% with EOC) from 161 centers were randomized. Baseline characteristics were balanced between arms; median age was 61 years, 96% had ECOG PS 0/1, 58% had no residual tumor, and 77% had high-grade serous histology. Serious adverse events of special interest for BEV occurred in 51/448 pts (11%) vs 61/442 pts (14%) receiving BEV15 vs BEV30, respectively: hypertension (2.7%/4.5%), thromboembolic event (2.2%/3.2%), fistula (3.1%/1.1%), gastrointestinal perforation (0.2%/0.9%), proteinuria (0.7%/1.4%), hemorrhage (0.2%/0.9%), and myocardial infarction (0%/1.1%). Efficacy is shown in the table.

*Performed because of evidence of nonproportional hazards, restricted at the time point of the last observed event (BEV15/BEV30).

结论：在原发性 EOC、FTC 或 PPC 患者中，持续 30 个月的 BEV 治疗既不能改善 PFS，也不能改善 OS。因此，15 个月的 BEV 治疗时间仍然是目前的标准。

Conclusions: Longer treatment with BEV for up to 30 months improves neither PFS nor OS in pts with primary EOC, FTC, or PPC. Therefore BEV treatment duration of 15 months remains standard of care.