National Cancer Center, Hospital East, Kashiwa, Chiba, Japan.
J Clin Oncol. 2011 Oct 20;29(30):3968-76. doi: 10.1200/JCO.2011.36.2236. Epub 2011 Aug 15.
The Avastin in Gastric Cancer (AVAGAST) trial was a multinational, randomized, placebo-controlled trial designed to evaluate the efficacy of adding bevacizumab to capecitabine-cisplatin in the first-line treatment of advanced gastric cancer.
Patients received bevacizumab 7.5 mg/kg or placebo followed by cisplatin 80 mg/m(2) on day 1 plus capecitabine 1,000 mg/m(2) twice daily for 14 days every 3 weeks. Fluorouracil was permitted in patients unable to take oral medications. Cisplatin was given for six cycles; capecitabine and bevacizumab were administered until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Log-rank test was used to test the OS difference.
In all, 774 patients were enrolled; 387 were assigned to each treatment group (intention-to-treat population), and 517 deaths were observed. Median OS was 12.1 months with bevacizumab plus fluoropyrimidine-cisplatin and 10.1 months with placebo plus fluoropyrimidine-cisplatin (hazard ratio 0.87; 95% CI, 0.73 to 1.03; P = .1002). Both median progression-free survival (6.7 v 5.3 months; hazard ratio, 0.80; 95% CI, 0.68 to 0.93; P = .0037) and overall response rate (46.0% v 37.4%; P = .0315) were significantly improved with bevacizumab versus placebo. Preplanned subgroup analyses revealed regional differences in efficacy outcomes. The most common grade 3 to 5 adverse events were neutropenia (35%, bevacizumab plus fluoropyrimidine-cisplatin; 37%, placebo plus fluoropyrimidine-cisplatin), anemia (10% v 14%), and decreased appetite (8% v 11%). No new bevacizumab-related safety signals were identified.
Although AVAGAST did not reach its primary objective, adding bevacizumab to chemotherapy was associated with significant increases in progression-free survival and overall response rate in the first-line treatment of advanced gastric cancer.
阿瓦斯汀胃癌试验（AVAGAST）是一项多中心、随机、安慰剂对照试验，旨在评估贝伐单抗联合卡培他滨和顺铂在晚期胃癌一线治疗中的疗效。
患者接受贝伐单抗 7.5mg/kg 或安慰剂，随后在第 1 天给予顺铂 80mg/m2，同时给予卡培他滨 1000mg/m2，每日 2 次，连用 14 天，每 3 周 1 个周期。不能口服药物的患者允许使用氟尿嘧啶。顺铂使用 6 个周期；卡培他滨和贝伐单抗一直使用到疾病进展或不可接受的毒性。主要终点是总生存期（OS）。采用对数秩检验比较 OS 差异。
共纳入 774 例患者；按意向治疗人群分为 387 例贝伐单抗联合氟嘧啶-顺铂组和 387 例安慰剂联合氟嘧啶-顺铂组，共观察到 517 例死亡。贝伐单抗联合氟嘧啶-顺铂组的中位 OS 为 12.1 个月，安慰剂联合氟嘧啶-顺铂组为 10.1 个月（风险比 0.87；95%CI，0.73 至 1.03；P =.1002）。贝伐单抗组的中位无进展生存期（6.7 个月比 5.3 个月；风险比 0.80；95%CI，0.68 至 0.93；P =.0037）和总缓解率（46.0%比 37.4%；P =.0315）均显著优于安慰剂组。预先计划的亚组分析显示，疗效结果存在区域性差异。最常见的 3 至 5 级不良事件为中性粒细胞减少症（贝伐单抗联合氟嘧啶-顺铂组 35%，安慰剂联合氟嘧啶-顺铂组 37%）、贫血（10%比 14%）和食欲下降（8%比 11%）。未发现新的贝伐单抗相关安全性信号。
尽管 AVAGAST 未达到主要目标，但在晚期胃癌的一线治疗中，贝伐单抗联合化疗可显著提高无进展生存期和总缓解率。
