LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib

Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.

Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.

Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.

Progression-Free Survival (PFS) was defined as the time from randomization to the earliest occurrence of disease progression or death from any cause. Per RECIST v1.0, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants with symptomatic progression, even without radiological confirmation, were also counted. Those who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Participants who received non-study anti-cancer therapies before progression were also censored.

A participant was considered a responder if they had achieved either a complete response (CR), defined as the disappearance of all target and non-target lesions, or a partial response (PR), defined as at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, as assessed by the investigator and confirmed by radiographic imaging within four weeks of the initial observation.

Clinical Benefit (CB) was defined as evidence of a complete response (CR), partial response (PR), or stable disease (SD). CR referred to the disappearance of all target and non-target lesions, PR to at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, and SD to neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression, based on the smallest sum of diameters recorded since treatment initiation. All assessments were made by the investigator.

Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator.

Duration of Response (DOR) was defined as the time from the first documented evidence of a complete response (CR) or partial response (PR) until the first recorded sign of disease progression or death from any cause. According to RECIST, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Those who received non-study anti-cancer therapies before progression were also censored.

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its causal relationship. This included any unfavorable or unintended sign (such as abnormal lab findings), symptom, or disease, whether new or worsened. A Serious Adverse Event (SAE) was defined as any such occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury.

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its relationship to the product. This included any unfavorable or unintended sign (such as abnormal lab results), symptom, or disease, whether new or worsened. The severity of AEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).

A Serious Adverse Event (SAE) was defined as any such occurrence that resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury. The severity of SAEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).

The EORTC QLQ-C30 is a comprehensive questionnaire developed for assessing the quality of life of cancer patients across different aspects including function scales namely physical, role, cognitive, emotional and social; symptom scales such as fatigue, pain, nausea and vomiting; and a global scale pronouncing overall health status. Its scoring method involves a 4-point Likert scale (ranging from 1 'Not at all' to 4 'Very Much'). Domain scores are calculated by averaging the items within the respective domain and then linearly transforming the score to fit within a 0-100 scale to finalize the scores. In terms of interpretation, a high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

The QLQ-STO22 consists of 22 items divided into five subscales: dysphagia, pain, reflux, eating restrictions and anxiety, as well as single items addressing dry mouth, body image, taste, and hair loss. Each item is answered on a 4-point scale, ranging from 1 (not at all) to 4 (very much). Raw scores for each subscale or single item are calculated by averaging the scores of the individual items that make up the scale. These scores are then linearly transformed to range from 0 to 100. In terms of interpretation, a higher score indicates a worse quality of life concerning the specific symptoms assessed.

The EQ-5D is a standardized instrument developed by the EuroQoL Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score.

The Utility Score (Health Utility Index) is derived from the five dimensions of the EQ-5D descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has levels indicating severity (e.g., 1 = no problems, 2 = some problems, 3 = extreme problems). These combinations form a health state, which is then converted into a single index value using a country-specific value set. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1.0, where: 1.0 = perfect health, 0 = death and < 0 = health states considered worse than death.

The EQ-5D is a standardized instrument developed by the EuroQol Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score.

The Thermometer Score is a self-rated health score using a vertical visual analogue scale , where respondents rate their overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).

The severity of chemistry parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening).

Chemistry data included: Alanine aminotransferase (ALT), Albumin, Alkaline phosphatases (ALP), Aspartate aminotransferase (AST), Calcium (hypercalcemia), Calcium (hypocalcemia), Creatine Kinase (CK), Creatine, Glucose (hyperglycemia), Glucose (hypoglycemia), Magnesium (hypermagnesemia), Magnesium (hypomagnesemia), Potassium (hyperkalemia), Potassium (hypokalemia), Sodium (hypernatremia), Sodium (hyponatremia) and Total Bilirubin.

The severity of hematologic parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening).

Hematology data included: Hemoglobin, Platelet count, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) and White Blood Cell count.