ToGA Study - A Study of Herceptin (Trastuzumab) in Combination With Chemotherapy Compared With Chemotherapy Alone in Patients With HER2-Positive Advanced Gastric Cancer

PFS was defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.

The median time, in months, from the date of randomization to the date of a PFS event. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.

TTP was defined as the time from the date of randomization and the date of the first occurrence of PD. Participants were censored at the last date of tumor assessment, the last date in the study drug log, or the last date of follow-up.

The median time, in months, from the date of randomized to the date of a TTP event. Participants were censored at the last date of tumor assessment, the last date in the study drug log, or the last date of follow-up.

For TLs, a CR was defined as the disappearance of all TLs and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels.

Duration of response was defined for responders as the time from the date on which the CR or PR was first recorded to the date on which PD is first noted. Participants were censored on the date of death, the date of last tumor measurement, the last date in study drug log, or the date of last follow-up.

The median time, in months, of the duration of response. Participants were censored at the date of death, the date of last tumor measurement, the last date in study drug log, or the date of last follow-up.

Clinical benefit was defined as stable disease (SD), CR, or PR for 6 weeks or longer as determined by RECIST. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as a reference the smallest SLD recorded since treatment had started. For NTLs, SD was defined as a persistence of one or more NTLs and/or maintenance of tumor marker levels above the normal limits.

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score equals (=) better level of functioning or greater degree of symptoms.

The QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.

The participant assessed their pain on a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.

Analgesic medications were recorded throughout the study until disease progression.

Change in body weight was categorized as an increase of greater than (>)5 percent (%), no change (plus or minus [±]5%), decrease of >5-10%, or a decrease of >10% from BL to the end of study. Time windows were applied in order to assign visits to weight measurements, and the lowest post-screening value recorded was used for the analysis. The percentage change in weight from screening was summarized over time.

Individual steady state predicted exposure, as assessed by median AUC (measured as mg multiplied by [*] day per liter [L]) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion. Individual steady state AUC was calculated using all available PK samples from all timepoints.

Median Cmin (measured as milligrams per liter [mg/L]) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion.

Median Cmax (measured as mg/L) calculated for all treated participants using the nominal dosage schedule administered as an IV infusion.