Seoul National University College of Medicine, Seoul, South Korea.
Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19.
Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2; also known as ERBB2), was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer.
ToGA (Trastuzumab for Gastric Cancer) was an open-label, international, phase 3, randomised controlled trial undertaken in 122 centres in 24 countries. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation. Participants were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab. Allocation was by block randomisation stratified by Eastern Cooperative Oncology Group performance status, chemotherapy regimen, extent of disease, primary cancer site, and measurability of disease, implemented with a central interactive voice recognition system. The primary endpoint was overall survival in all randomised patients who received study medication at least once. This trial is registered with ClinicalTrials.gov, number NCT01041404.
594 patients were randomly assigned to study treatment (trastuzumab plus chemotherapy, n=298; chemotherapy alone, n=296), of whom 584 were included in the primary analysis (n=294; n=290). Median follow-up was 18.6 months (IQR 11-25) in the trastuzumab plus chemotherapy group and 17.1 months (9-25) in the chemotherapy alone group. Median overall survival was 13.8 months (95% CI 12-16) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0.74; 95% CI 0.60-0.91; p=0.0046). The most common adverse events in both groups were nausea (trastuzumab plus chemotherapy, 197 [67%] vs chemotherapy alone, 184 [63%]), vomiting (147 [50%] vs 134 [46%]), and neutropenia (157 [53%] vs 165 [57%]). Rates of overall grade 3 or 4 adverse events (201 [68%] vs 198 [68%]) and cardiac adverse events (17 [6%] vs 18 [6%]) did not differ between groups.
Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer.
F Hoffmann-La Roche.
曲妥珠单抗是一种针对人表皮生长因子受体 2（HER2；也称为 ERBB2）的单克隆抗体，已被研究用于联合化疗作为 HER2 阳性晚期胃或胃食管交界处癌的一线治疗。
ToGA（曲妥珠单抗治疗胃癌）是一项在 24 个国家的 122 个中心进行的开放性、国际、3 期、随机对照试验。符合条件的患者为肿瘤组织 HER2 蛋白过表达（免疫组织化学检测）或基因扩增（荧光原位杂交检测）的胃或胃食管交界处癌患者。患者以 1:1 的比例随机分配接受化疗方案（卡培他滨加顺铂或氟尿嘧啶加顺铂，每 3 周给药 6 个周期）或化疗联合静脉注射曲妥珠单抗。分层因素包括东部肿瘤协作组体能状态、化疗方案、疾病程度、原发肿瘤部位和疾病可测量性，通过中央交互式语音识别系统进行随机分配。主要终点是所有接受至少一次研究药物治疗的随机患者的总生存期。该试验在 ClinicalTrials.gov 注册，编号为 NCT01041404。
594 名患者被随机分配至研究治疗组（曲妥珠单抗联合化疗，n=298；化疗单药组，n=296），其中 584 名患者纳入主要分析（n=294；n=290）。曲妥珠单抗联合化疗组的中位随访时间为 18.6 个月（IQR 11-25），化疗单药组为 17.1 个月（9-25）。接受曲妥珠单抗联合化疗的患者中位总生存期为 13.8 个月（95%CI 12-16），而接受化疗单药的患者为 11.1 个月（10-13）（风险比 0.74；95%CI 0.60-0.91；p=0.0046）。两组最常见的不良反应均为恶心（曲妥珠单抗联合化疗组 197 例[67%] vs 化疗单药组 184 例[63%]）、呕吐（曲妥珠单抗联合化疗组 147 例[50%] vs 化疗单药组 134 例[46%]）和中性粒细胞减少（曲妥珠单抗联合化疗组 157 例[53%] vs 化疗单药组 165 例[57%]）。两组的总体 3 级或 4 级不良反应发生率（201 例[68%] vs 198 例[68%]）和心脏不良事件发生率（17 例[6%] vs 18 例[6%]）无差异。
曲妥珠单抗联合化疗可作为 HER2 阳性晚期胃或胃食管交界处癌患者的新治疗标准。
罗氏公司。
