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
- PMID: 20728210
- DOI: 10.1016/S0140-6736(10)61121-X
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
Erratum in
- Lancet. 2010 Oct 16;376(9749):1302
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.
Copyright 2010 Elsevier Ltd. All rights reserved.
Comment in
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Cancer research in the global village.Lancet. 2010 Aug 28;376(9742):659-60. doi: 10.1016/S0140-6736(10)61022-7. Epub 2010 Aug 19. Lancet. 2010. PMID: 20728211 No abstract available.
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Targeted therapies: New standard of therapy for HER2-positive gastric cancers?Nat Rev Clin Oncol. 2010 Nov;7(11):611. doi: 10.1038/nrclinonc.2010.161. Nat Rev Clin Oncol. 2010. PMID: 21049571 No abstract available.
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Adding trastuzumab to standard chemotherapy in HER2-positive esophagogastric adenocarcinoma: a further step toward personalized medicine.Gastroenterology. 2011 Jan;140(1):356-8; discussion 358. doi: 10.1053/j.gastro.2010.11.011. Epub 2010 Nov 16. Gastroenterology. 2011. PMID: 21087674 No abstract available.
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Trastuzumab for gastric cancer treatment.Lancet. 2010 Nov 20;376(9754):1735; author reply 1735-6. doi: 10.1016/S0140-6736(10)62125-3. Lancet. 2010. PMID: 21093641 No abstract available.
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Trastuzumab for HER2-positive gastric and gastroesophageal junction cancers.Biomark Med. 2010 Dec;4(6):793. Biomark Med. 2010. PMID: 21174864 No abstract available.
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