Bang 2010.
Methods | International RCT (122 centers in 24 countries), Phase III | |
Participants |
Number of participants: 594 (September 2005 to June 2010 ) Number randomized: Experimental group (Trastuzumab in combination with fluoropyrimidine and cisplatin): 298 Control group (fluoropyrimidine and cisplatin): 296 Number evaluated: Experimental group: 294, age (mean ± SD): 59.4 ± 10.8 years Control group: 290, age (mean ± SD): 58.5 ± 11.2 years Diagnosis: Patients with gastric or gastro‐esophageal junction cancer were eligible for inclusion if their tumors showed over‐expression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in situ hybridization Inclusion: eligible patients should: be ≥ 18 years of age; histologically‐confirmed inoperable locally‐advanced, recurrent, or metastatic adenocarcinoma of the stomach or gastro‐esophageal junction; ECOG performance status 0 – 2; adequate organ function; and measurable or non‐measurable disease; tumors were centrally tested for HER2 status with immunohistochemistry (HercepTest, Dako, Denmark) and fluorescence in situ hybridization (FISH; HER2 FISH pharmDx, Dako) |
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Interventions |
Experimental group : D1 trastuzumab 8 mg/kg i.v. for cycle 1, and then 6 mg/kg i.v. Q3W until disease progression; D1 ‐ 5 800 mg/m² fluorouracil i.v., Q3W for 6 cycles; D1 80 mg/m² cisplatin i.v., Q3W for 6 cycles; D1 ‐ 15 1000 mg/m² capecitabine by mouth twice daily, every 3 weeks for 6 cycles Control group: D1 ‐ 5 800 mg/m² fluorouracil i.v., every 3 weeks for 6 cycles; D1 80 mg/m² cisplatin i.v., every 3 weeks for 6 cycles; D1 ‐ 15 1000 mg/m² capecitabine by mouth twice daily, every three weeks for 6 cycles |
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Outcomes |
Duration of follow‐up (median): 18.6 months (IQR 11 ‐ 25) for experimental group, 17.1 (IQR 9 ‐ 25) for control group OS, FPS, overall response, adverse events |
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Notes | Sponsor: Hoffmann‐La Roche The sponsor was involved in the study design, data collection, data analysis, results interpretation, and manuscript preparation Study referred to as "ToGA" |
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Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | "The randomisation sequence was created by F Hoff mann‐La Roche" |
Allocation concealment (selection bias) | Low risk | "Treatment was assigned by use of a randomised block design with block sizes of four patients, via a central interactive voice recognition system (by telephone)" |
Blinding of participants and personnel (performance bias) All outcomes | High risk | The open‐label design may introduce performance bias (e.g. through stress‐related mechanisms) |
Blinding of outcome assessment (detection bias) OS, Serious adverse events | Low risk | These outcomes were unlikely to be affected by the blinding status of assessors |
Blinding of outcome assessment (detection bias) PFS, Response, quality of life & adverse events | Low risk | "Efficacy and safety data were monitored by an independent data monitoring committee." |
Incomplete outcome data (attrition bias) All outcomes | Low risk | 584 randomized participants were included in analysis (98.3%) |
Selective reporting (reporting bias) | Low risk | Prior protocol was available |
Other bias | Low risk | No obvious potential source of bias |