背景：GOG-0218 建立了晚期卵巢癌標準一線化療每 3 周（q3w）加入 BEV 15mg/kg，持續 15 個月，但最佳 BEV 持續時間仍不清楚。我們報告了一項旨在解決這個問題的隨機 3 期臨床試驗的初步結果。

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：符合條件的 FIGO IIB-IV 期 EOC、FTC 或 PPC 和 ECOG PS#2 患者接受一期細胞減滅術，然後接受 6個周期的化療（紫杉醇175mg/m2+卡鉑 AUC 5Q3W）和 BEV（15mg/kg q3w）。患者隨機接受 BEV 治療 15個月（標準組 BEV15）或 30 個月（實驗組 BEV30），按 FIGO 分期/殘留腫瘤（IIB-IIIC 期/無殘留腫瘤與 IIB-IIIC期/殘留腫瘤或 IV 期）分層。主要終點研究者根據 recistv1.1 評估無進展生存率（PFS）。次要終點是總生存率（OS）、客觀有效率、生活質量、安全性和耐受性。該試驗設計了 80.2%的功率來檢測有利於 BEV30（雙側對數秩）的危險比（HR）為 0.66，5%顯著性水平，10%退出率）後 697 PFS 事件。這項試驗是由 F。Hoffmann La Roche 有限公司，根據 ENGOT 模型 A 執行。

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.

結果：從 2011 年 11 月到 2013 年 8 月，來自 161 個中心的 927 名女性（83%患有 EOC）被隨機分組。基線特征在兩組之間保持平衡；中位年齡 61 歲，96%有 Ecog/Ps:0/1，58%無腫瘤殘留，77%有高級別漿膜組織學。兩組（BEV15 Vs BEV30）嚴重的不良事件分別為 51/448 例患者（11%）與 61/442 例患者（14%）：高血壓（2.7%/4.5%）、血栓栓塞事件（2.2%/3.2%）、瘺（3.1%/1.1%）、胃腸道穿孔（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%）。療效見下表。

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).

結論：在原發性 EOC、FTC 或 PPC 患者中，持續 30 個月的 BEV 治療既不能改善 PFS，也不能改善 OS。因此，15 個月的 BEV 治療時間仍然是目前的標準。

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.