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
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.
Copyright 2010 Elsevier Ltd. All rights reserved.