Lancet:曲妥单抗联合化疗VS普通化疗治疗HER2阳性晚期胃癌或食管胃结合部腺癌：3期随机对照开放试验

来源：MedSci原创

Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial.

Bang YJ, Van Cutsem E, Feyereislova A, et al.

Lancet. 2010 Aug 28;376(9742):687-97

曲妥单抗联合化疗VS普通化疗治疗HER2阳性晚期胃癌或食管胃结合部腺癌：3期随机对照开放试验

曲妥单抗是一种拮抗癌症细胞人表皮生长因子受体2（HER2）蛋白的药物。过量HER2蛋白会促使癌症细胞快速生长，从而影响化学疗法的有效性。晚期胃癌或食管胃结合部腺癌（G/GEJ）仍是治疗相当困难的疾病，治疗有效率和存活率很低。HER2蛋白是该肿瘤的标志物之一。在这项治疗HER2蛋白高表达G/GEJ的随机对照试验中，曲妥单抗联合化疗组的总体生存率优于普通化疗组。这项大型试验首次证实了HER2靶向治疗对于G/GEJ的有效性。HER2蛋白检测应成为G/GEJ治疗中的常规标准，对于HER2蛋白阳性患者，应采用曲妥单抗联合化疗以改善预后。

Abstract

BACKGROUND: 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.

METHODS: 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.

FINDINGS: 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.

INTERPRETATION: 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.

FUNDING: F Hoffmann-La Roche.