» Articles » PMID: 20728210

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

Overview
Journal Lancet
Publisher Elsevier
Specialty General Medicine
Date 2010 Aug 24
PMID 20728210
Citations 3299
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Chemotherapy Options for Locally Advanced Gastric Cancer: A Review.

Semenova Y, Kerimkulov A, Uskenbayev T, Zharlyganova D, Shatkovskaya O, Sarina T Cancers (Basel). 2025; 17(5).

PMID: 40075656 PMC: 11899121. DOI: 10.3390/cancers17050809.


Proteomic characterization of MET-amplified esophageal adenocarcinomas reveals enrichment of alternative splicing- and androgen signaling-related proteins.

Grothey B, Lyu S, Quaas A, Simon A, Jung J, Schroder W Cell Mol Life Sci. 2025; 82(1):112.

PMID: 40074836 PMC: 11904063. DOI: 10.1007/s00018-025-05635-7.


Biomarkers in gastroesophageal cancer 2025: an updated consensus statement by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).

Alsina Maqueda M, Teijo Quintans A, Cuatrecasas M, Fernandez Acenero M, Fernandez Montes A, Gomez Martin C Clin Transl Oncol. 2025; .

PMID: 40072752 DOI: 10.1007/s12094-025-03865-6.


Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients.

He L, Liu B, Wang Z, Han Q, Chen H Curr Treat Options Oncol. 2025; .

PMID: 40056280 DOI: 10.1007/s11864-025-01300-0.


Reversal of chemotherapy resistance in gastric cancer with traditional Chinese medicine as sensitizer: potential mechanism of action.

Zhou C, Wu K, Gu M, Yang Y, Tu J, Huang X Front Oncol. 2025; 15:1524182.

PMID: 40052129 PMC: 11882405. DOI: 10.3389/fonc.2025.1524182.