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

Yung Jue Bang, Eric Van Cutsem, Andrea Feyereislova, Hyun C. Chung, Lin Shen, Akira Sawaki, Florian Lordick, Atsushi Ohtsu, Yasushi Omuro, Taroh Satoh, Giuseppe Aprile, Evgeny Kulikov, Julie Hill, Michaela Lehle, Josef Rüschoff, Yoon Koo Kang

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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. Interpretaion 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.

Original languageEnglish
Pages (from-to)687-697
Number of pages11
JournalThe Lancet
Volume376
Issue number9742
DOIs
Publication statusPublished - 2010 Aug 28

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Esophageal Neoplasms
Combination Drug Therapy
Stomach
Randomized Controlled Trials
Drug Therapy
Therapeutics
Cisplatin
Trastuzumab
Survival
Gene Amplification
Random Allocation
Neutropenia
Fluorescence In Situ Hybridization
Fluorouracil
Nausea
Stomach Neoplasms
Vomiting
Neoplasms
Immunohistochemistry
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Bang, Yung Jue ; Van Cutsem, Eric ; Feyereislova, Andrea ; Chung, Hyun C. ; Shen, Lin ; Sawaki, Akira ; Lordick, Florian ; Ohtsu, Atsushi ; Omuro, Yasushi ; Satoh, Taroh ; Aprile, Giuseppe ; Kulikov, Evgeny ; Hill, Julie ; Lehle, Michaela ; Rüschoff, Josef ; Kang, Yoon Koo. / 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. In: The Lancet. 2010 ; Vol. 376, No. 9742. pp. 687-697.
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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. Interpretaion 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.",
author = "Bang, {Yung Jue} and {Van Cutsem}, Eric and Andrea Feyereislova and Chung, {Hyun C.} and Lin Shen and Akira Sawaki and Florian Lordick and Atsushi Ohtsu and Yasushi Omuro and Taroh Satoh and Giuseppe Aprile and Evgeny Kulikov and Julie Hill and Michaela Lehle and Josef R{\"u}schoff and Kang, {Yoon Koo}",
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Bang, YJ, Van Cutsem, E, Feyereislova, A, Chung, HC, Shen, L, Sawaki, A, Lordick, F, Ohtsu, A, Omuro, Y, Satoh, T, Aprile, G, Kulikov, E, Hill, J, Lehle, M, Rüschoff, J & Kang, YK 2010, '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', The Lancet, vol. 376, no. 9742, pp. 687-697. https://doi.org/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. / Bang, Yung Jue; Van Cutsem, Eric; Feyereislova, Andrea; Chung, Hyun C.; Shen, Lin; Sawaki, Akira; Lordick, Florian; Ohtsu, Atsushi; Omuro, Yasushi; Satoh, Taroh; Aprile, Giuseppe; Kulikov, Evgeny; Hill, Julie; Lehle, Michaela; Rüschoff, Josef; Kang, Yoon Koo.

In: The Lancet, Vol. 376, No. 9742, 28.08.2010, p. 687-697.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA)

T2 - A phase 3, open-label, randomised controlled trial

AU - Bang, Yung Jue

AU - Van Cutsem, Eric

AU - Feyereislova, Andrea

AU - Chung, Hyun C.

AU - Shen, Lin

AU - Sawaki, Akira

AU - Lordick, Florian

AU - Ohtsu, Atsushi

AU - Omuro, Yasushi

AU - Satoh, Taroh

AU - Aprile, Giuseppe

AU - Kulikov, Evgeny

AU - Hill, Julie

AU - Lehle, Michaela

AU - Rüschoff, Josef

AU - Kang, Yoon Koo

PY - 2010/8/28

Y1 - 2010/8/28

N2 - 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. Interpretaion 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.

AB - 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. Interpretaion 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.

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