Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer

OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death were censored at last follow-up or cut-off date, whichever comes first. OS was estimated by Kaplan-Meier method.

Time frame: From the date of randomization to the data cut-off date (maximum duration: up to approximately 46 months)

Population: Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.

Any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study medication was considered an adverse event (AE). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs/TESAEs were defined as events that started on or after treatment or started before treatment and worsened after the start of treatment through 30 days after the last dose of study treatment.

Time frame: From the first dose of study treatment until 30 days after the last dose of study treatment (maximum duration: up to approximately 46 months)

Population: Analysis was performed on the As-treated (AT) population that included all participants who received at least 1 dose of study treatment.

PFS was defined as the time from randomization until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for target lesions were defined as target lesions with at least 20 % relative increase in the sum of diameters with reference to the smallest sum on study, including the baseline sum and this sum demonstrated an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions or Unequivocal progression of existing non-target lesions. All alive participants with no disease progression as of the analysis cut-off date were censored at the last tumor assessment. PFS was estimated by Kaplan-Meier method.

Time frame: From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months)

Population: Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.

EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) and other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health and QoL, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 and 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best QoL for participant.

Time frame: Baseline, Day 1 Cycle 2 up to end of treatment (EOT) (within 30 days of last study treatment) and 30-Day safety follow-up visit (maximum duration: up to approximately 46 months)

Population: Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered. Here, 'number analyzed' = participants with available data for each specified category.

DCR was defined as the proportion of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD). The assessment of DCR was based on Investigator review of radiologic images and following RECIST criteria (version 1.1, 2009).

Time frame: From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks

Population: Analysis was performed on TR population that included participants in the ITT population that met 2 criteria: had measurable disease (at least 1 target lesion) at baseline; had at least 1 post-baseline evaluation or early disease progression/cancer-related death occurred before first evaluation on treatment (post-baseline).

The Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) assessed symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, dietary restrictions, pain QS22, reflux, and anxiety) and 4 single items (dry mouth, hair loss, taste problems, body image). Most questions use 4-point scale (1='Not at all', 2=a little, 3=quite a bit and 4='Very much'). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100, where higher score=better level of functioning or greater degree of symptoms.

Time frame: Baseline, Cycle 1 Day 1 up to end of treatment (EOT) (within 30 days of last study treatment) (maximum duration: up to approximately 46 months)

Population: Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.

Overall response rate was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to \< 10 mm. PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference.

Time frame: From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months), assessed every 8 weeks

Population: Analysis was performed on tumor response (TR) population that included participants in the ITT population that met 2 criteria: had measurable disease (at least 1 target lesion) at baseline; had at least 1 post-baseline evaluation or early disease progression/cancer-related death occurred before first evaluation on treatment (post-baseline).

The ECOG performance status was used to evaluate participant's disease progression and the effect of the disease on the participant's activities of daily living. It ranges on the scale from 0-5 (0 = normal activity; 1= symptoms but ambulatory; 2= in bed for \< 50% of the time; 3= in bed for \> 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG performance status score from baseline was defined as a change from 0, 1 to \>=2, or from 2 to \>=3.

Time frame: At the time of randomization (Day 1 Cycle 1) and within 24 hours prior to start of study treatment in every cycle (maximum duration: up to approximately 46 months)

Population: Analysis was performed on the ITT population that included all randomized participants, regardless of whether or not study treatment was administered.