Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study
Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study
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DOI：
10.1200/jco.2011.36.2236
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发表时间：
2011-10-20
影响因子：
45.3
通讯作者：
Kang, Yoon-Koo
中科院分区：
文献类型：
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作者：
Ohtsu, Atsushi;Shah, Manish A.;Kang, Yoon-Koo
目的阿瓦斯汀治疗胃癌 (AVAGAST) 试验是一项多国、随机、安慰剂对照试验，旨在评估卡培他滨-顺铂一线治疗晚期胃癌时添加贝伐单抗的疗效。患者和方法患者接受贝伐单抗 7.5 mg/kg 或安慰剂，随后接受顺铂 80 mg/m(2)。 1 加卡培他滨 1,000 mg/m(2)，每日两次，每 3 周持续 14 天。不能口服药物的患者允许使用氟尿嘧啶。给予顺铂六个周期；给予卡培他滨和贝伐单抗直至疾病进展或出现不可接受的毒性。主要终点是总生存期（OS）。采用对数秩检验来检验 OS 差异。结果 共有 774 名患者入组； 387 人被分配到每个治疗组（意向治疗人群），观察到 517 人死亡。贝伐单抗加氟嘧啶-顺铂的中位 OS 为 12.1 个月，安慰剂加氟嘧啶-顺铂的中位 OS 为 10.1 个月（风险比 0.87；95% CI，0.73 至 1.03；P = .1002）。与安慰剂相比，贝伐珠单抗的中位无进展生存期（6.7 个月 vs 5.3 个月；风险比，0.80；95% CI，0.68 至 0.93；P = 0.0037）和总体缓解率（46.0% vs 37.4%；P = 0.0315）均显着改善。预先计划的亚组分析揭示了疗效结果的区域差异。最常见的 3 至 5 级不良事件是中性粒细胞减少症（35%，贝伐单抗加氟嘧啶-顺铂；37%，安慰剂加氟嘧啶-顺铂）、贫血（10% vs 14%）和食欲下降（8% vs 11%）。没有发现新的贝伐珠单抗相关安全信号。结论虽然 AVAGAST 没有达到其主要目标，但在化疗中添加贝伐珠单抗与晚期胃癌一线治疗中无进展生存期和总体缓解率的显着增加相关。
PurposeThe 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 and MethodsPatients 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.ResultsIn 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.ConclusionAlthough 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.