ToGA TRIAL PUBLISHED

Lancet. 2010 Aug 19. [Epub ahead of print]

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, 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; for the ToGA Trial Investigators.

Seoul National University College of Medicine, Seoul, South Korea.

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.