Hecht 2013.

Methods	International RCT (186 centers in 22 countries), Phase III
Participants	Number of participants: 545 (June 2008 to January 2012) Number randomized: Experimental group (oxaliplatin and capecitabine + lapatinib): 272 Control group (oxaliplatin and capecitabine + placebo): 273 Number evaluated: Experimental group: 249, age (median and range): 61 (19 ‐ 86) years Control group: 238, age (median and range): 59 (27 ‐ 84) years Diagnosis: ErbB2 (HER2)‐positive patients with histologically‐confirmed locally‐advanced unresectable or metastatic adenocarcinoma of the stomach, esophagus or gastro‐esophageal junction Inclusion: eligible patients should: have signed informed consent; have histologically‐confirmed gastric, esophageal, or gastro‐esophageal junction adenocarcinoma; disease that is locally advanced (unresectable), metastatic, or locally recurrent; Measurable or non‐measurable, but radiologically evaluable disease, according to RECIST; ErbB2 (HER2)‐positive; be aged 18+ years; ECOG performance status 0 ‐ 2; adequate organ function, including adequate hematologic, renal and liver function; cardiac ejection fraction within institutional range of normal as measured by echocardiogram; able to swallow and retain oral medications, and/or receive enteral medications via gastrectomy feeding tube; women and men with potential to have children must be willing to practise acceptable methods of birth control during the study; prior gastric surgery is permitted if > 3 weeks prior and recovered; prior chemotherapy for non‐gastric malignancy if > than 5 years; prior neoadjuvant and/or adjuvant chemotherapy for early‐stage gastric cancer if > 6 months since completion; at least 4 weeks since prior radiotherapy; prior biologic, hormonal, or immunologic cancer treatment if > 5 years since treatment
Interventions	Experimental group : D1 oxaliplatin 130 mg/m²; D1 ‐ 14 capecitabine 850 mg/m² twice daily; D1 ‐ 21 lapatinib 1250 mg/day Control group: D1 oxaliplatin 130 mg/m²; D1 ‐ 14 capecitabine 850 mg/m² twice daily; D1 ‐ 21 placebo daily
Outcomes	Duration of follow‐up (median): not mentioned OS, PFS, overall response, adverse events
Notes	Sponsored by GlaxoSmithKline (GSK) Initial study design had PFS as the primary endpoint with a sample size of 410 participants. In September 2009, the study was amended to change the primary endpoint to OS and increase sample size to 535 participants Reported in abstract form only
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomization code was created by the GlaxoSmithKline internal randomization system named Randall
Allocation concealment (selection bias)	Low risk	A randomization code was blinded to all project members and investigators and locked until unblinding in February 2013
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind (participant, caregiver, investigator, outcomes assessor)
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	Double blind (participant, caregiver, investigator, outcomes assessor)
Incomplete outcome data (attrition bias) All outcomes	Low risk	487 randomized participants were included in analysis (89.4%); ITT analysis
Selective reporting (reporting bias)	Low risk	Prior protocol was available
Other bias	Low risk	No obvious potential source of bias