Neoplasms, Gastrointestinal Tract
Conditions
Keywords
lapatinib, paclitaxel, ErbB2, Gastric cancer, Advanced gastric cancer
Brief summary
EGF104578 is two-part study (Pilot part/Randomized part).Pilot part is designed to find the optimal (best) doses of lapatinib and paclitaxel when given together,Randomized part is designed to evaluate the overall survival in patients receiving lapatinib and paclitaxel compared to patients receiving only paclitaxel.
Interventions
DRUGLapatinib
6 pills at 250 mg each once daily
DRUGPaclitaxel
Infusion at 80 mg/m2 weekly
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Specific Information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the Investigator's Brochure (IB) Pilot Part Subjects eligible for enrollment in the Pilot Part of the study must meet all of the following criteria: * Signed informed consent * Male or female; ≥ 20 years (at the time of giving consent) * Any histologically or cytologically confirmed gastric carcinoma independent of tumor ErbB2 status * Subjects who have received one prior regimen for gastric carcinoma and developed disease progression or recurrence. The regimen must have contained 5-fluoropyrimidine and/or cisplatin * Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by echocardiogram (ECHO). Multigated acquisition (MUGA) scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive (LVEF of ≥50% required if normal range of LVEF is not provided by institution) * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 * Able to swallow and retain oral medication * Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study * Washout period from the prior last therapy as follows; Chemotherapy (except for agents below) 4 weeks (I.V) Chemotherapy (except for agents below) 2 weeks (P.O) Trastuzumab, Bevacizumab 4 weeks Mitomycin-C, nitrosourea 6 weeks Radiotherapy, Immunotherapy, Biologic therapy and Surgery (except for minor surgical procedure) 2 weeks * Willing to complete all screening assessments as outlined in the protocol * Adequate organ function as defined in Table 2 Baseline Laboratory Values * Able to be hospitalized for PK analysis during cycle 1 * Life expectancy of at least 12 weeks from the first dose of study treatment) Randomized Part Subjects eligible for enrollment in the Randomized Part of the study must meet all of the following criteria: * Signed informed consent * Male or female; ≥ 20 years (at the time of giving consent) * Histologically or cytologically confirmed gastric carcinoma with documented amplification of ErbB2 by fluorescence in situ hybridization (FISH) in primary or metastatic tumor tissue * Subjects who received one prior regimen for gastric carcinoma and defined as progression disease. The regimen must be containing 5-fluoropyrimidine and/or cisplatin * Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors) * Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive (LVEF of ≥50% required if normal range of LVEF is not provided by institution) * ECOG Performance Status of 0 to 1 * Able to swallow and retain oral medication * Archived (or Biopsy ) tumor tissue available for FISH testing \[Wolff, 2007\] in central laboratory * Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study * Washout period from the prior last therapy as follows; Chemotherapy (except for agents below) 4 weeks (IV) Chemotherapy (except for agents below) 2 weeks (P.O) Trastuzumab, Bevacizumab 4 weeks Mitomycin-C, nitrosourea 6 weeks Radiotherapy, Immunotherapy, Biologic therapy and Surgery (except for minor surgical procedure) 2 weeks * Willing to complete all screening assessments as outlined in the protocol * Adequate organ function as defined in Table 2 * Gastrectomy status depending on the result in the Pilot Part * Life expectancy of at least 12 weeks from the first dose of study treatment Table 2 Baseline Laboratory Values SYSTEM LABORATORY (VALUES) Hematologic: ANC (absolute neutrophil count) Hemoglobin: Platelets (≥ 2.0 × 10\^9/L) (≥ 9 g/dL) (≥ 100 × 10\^9/L) Hepatic Albumin Serum bilirubin AST and ALT (≥ 2.5 g/dL) (≤ 1.25 x ULN) (≤ 2.5 × ULN without liver metastases) (≤ 5 × ULN if documented liver metastases) Renal Serum Creatinine Calculate Creatinine Clearance (see Section 11.3) (≤ 2.0 mg/dL) \- OR - (≥30 mL/min)
Exclusion criteria
Subjects meeting any of the following criteria must not be enrolled in the study: * Pregnant or lactating female at anytime during the study * Planned concurrent anti-cancer therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment * Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2) * Peripheral neuropathy of Grade 2 or greater * Malabsorption syndrome, disease significantly affecting gastrointestinal function. Subjects with ulcerative colitis and Crohn's disease are also excluded * History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, are eligible * Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety * Life threatening infection * Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent * Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure * Known history or clinical evidence of central nervous system (CNS) metastasis * Concurrent treatment with prohibited medications, including herbal remedies and Chinese traditional medicines * Concurrent treatment with an investigational agent within 28 days prior to the administration of paclitaxel and/or lapatinib * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to paclitaxel, including polyethoxylated castor oil, alcohol, or lapatinib or their excipients * Anamnesis or diagnosis of pulmonary disorder, such as interstitial pneumonia, pulmonary fibrosis or serious hypoxia * Gastrectomy surgery if Pilot Part of the study determines that partial gastrectomy (pylorus spared) or total/partial gastrectomy (pylorus removed) has a significant negative impact upon lapatinib PK and safety profile * Known history of use of any EGFR agent (except Trastuzumab) * Prior gastric cancer treatment which included a taxane.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study | 28 days | DLTs consisted of only drug-related toxicities (neurologic and non-neurologic DLTs). A neurologic DLT was defined as grade 3/4 clinically significant peripheral motor and/or sensitive neuropathy. Non-neurologic DLTs mainly included the following: grade 3/4 clinically significant non-hematological toxicity (except nausea), grade 4 neutropenia lasting \>=7 days, thrombocytopenia (\<=25000 cells per cubic millimeter), inability to begin next treatment within 2 weeks of scheduled dosing due to unresolved toxicity, treatment delay (due to toxicity) of \>5 days, for Days 8 or 15 of weekly paclitaxel. |
| Overall Survival (OS) in the Randomized Part of the Study | From randomization until death due to any cause (up to 42.58 months) | OS was defined as the time from randomization until death due to any cause. For participants who did not die, time to death was censored at the time of last contact. For censored participants, time to death was defined as the time from randomization to the time of last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study | Days 8 and 14 | PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14. AUC is defined as the area under the lapatinib concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after oral adminisation. |
| Cmax of Paclitaxel in the Pilot Part of the Study | Days 1 and 8 | PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. |
| Tmax of Paclitaxel in the Pilot Part of the Study | Days 1 and 8 | PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. |
| AUC(0-24) of Paclitaxel in the Pilot Part of the Study | Days 1 and 8 | PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from the start of infusion (time 0) to 24 hours after the start of the infusion. |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study | Days 1 and 8 | PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-inf) is area under the plasma concentration-time curve from the start of infusion (time 0) extrapolated to infinity. |
| Half-life of Paclitaxel in the Pilot Part of the Study | Days 1 and 8 | PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Half-life is defined as the time required for the amount of the drug in the plasma to decrease by half. |
| Clearance of Paclitaxel in the Pilot Part of the Study | Days 1 and 8 | PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Clearance is defined as the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time. |
| Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study | Days 1 and 8 | PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Vss is the volume of distribution at steady state of paclitaxel. |
| Progression-free Survival (PFS) in the Randomized Part of the Study | From randomization until disease progression or death due to any cause (up to 42.35 months) | PFS was defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. |
| Time to Progression in the Randomized Part of the Study | From randomization until disease progression or death due to disease (up to 42.35 months ) | Time to progression was defined as the time from randomization until the earliest date of disease progression or death due to disease. Per RECIST, version 1.0, PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. |
| Percentage of Participants With Overall Response in the Randomized Part of the Study | From randomization up to 5.62 months | Overall response was defined as the percentage of participants achieving either complete response (CR) or partial response (PR). Per RECIST, version 1.0, CR was defined as the disappearance of all target lesions, and PR was defined as a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. |
| Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | up to 5.62 months | Time to response was defined as the time from randomization to CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD). For participants who did not achieve a CR or PR, time to response was censored at the last assessment prior to other cancer therapies. For censored participants, time to response was defined as the time from randomization to the time of the last assessment prior to the administation of other cancer therapies. |
| Duration of Response in the Randomized Part of the Study | up to 18.27 months | Duration of response was defined as the time from the first documented evidence of CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD) until the first documented sign of disease progression (at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions) or death due to any cause, if sooner. |
| Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | From the first dose of investigational product to 30 days after the last dose (up to 110.3 weeks in the Randomized part) | The Common Terminology Criteria for Advere Events (CTCAE) is a descriptive terminology that can be used for AE reporting. Grade (G) refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade (G) refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE. |
| Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QOL Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems. |
| Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study | Days 8 and 14 | Pharmacokinetic (PK) samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14. |
| Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study | Pretreatment | EGFR protein expression on the surface of cells in gastric cancer tissue samples was measured using a moncolonal antibody specific for the extracellular region of EGFR, and the degree of membrane staining was evaluated. 3+ indicates positive EGFR expression; \<3+ indicates negative EGFR expression. |
| Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study | Pretreatment | HER2 protein expression on the surface of cells in gastric cancer tissue samples was measured using a monoclonal antibody specific for the extracellulr region of HER2, and the degree of membrane staining was evaulated. The immunohistochemistry test gives a score of 0 to 3+ and measures the amount of HER2 receptor protein on the surface of cells in a gastric cancer tissue sample. Score of 0 to 1+, HER2 negative; score of 2+, borderline; score of 3+, HER2 positive. |
| Number of Participants With Mutations That May Correlate With Response and Toxicity to Lapatinib | Pretreatment | An inadequate number of tissue samples were obtained; thus, analysis could not be performed. |
| Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study | Baseline and end of therapy (up to 42.58 months) | The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function. |
| Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study | Days 8 and 14 | PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14. |
Countries
China, Japan, South Korea, Taiwan
Participant flow
Recruitment details
This study consisted of a Pilot part and a Randomized part. The Pilot part and the Randomized part had two separate participant (par.) populations. The study period of the Randomized part was from 31 March 2008 to 5 January 2012 (cut-off date for efficacy). Follow-up was conducted until 30 October 2012 (cut-off date for safety analysis).
Pre-assignment details
In the Pilot part, par. were enrolled in this study based on their gastrectomy status: non-gastrectomy (intact stomach), partial gastrectomy (gastrectomy with pylorus preserved), and gastrectomy (pylorus removed). However, no par. with partial gastrectomy were enrolled. In the Randomized part, par. were randomized to two treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants In the Pilot part, participants with non-gastrectomy (intact stomach) received 1500 milligrams (mg) of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg per square meters (m\^2). | 6 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants In the Pilot part, participants with gastrectomy (pylorus removed) received 1500 mg of oral lapatinib once daily throughout the study duration (lapatinib was not administered on Day 1 of the first cycle). Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2. | 6 |
| Lapatinib Plus Paclitaxel in Randomized Part Participants received 1500 mg of oral lapatinib once daily throughout the study duration. Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle). | 132 |
| Paclitaxel Alone in Randomized Part Participants received a paclitaxel 1-hour intravenous infusion weekly for 3 weeks of a 4-week cycle at 80 mg/m\^2 (on Days 1, 8, and 15 of each cycle). | 129 |
| Total | 273 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Pilot Part | Adverse Event | 4 | 0 | 5 | 0 | 0 |
| Pilot Part | Disease Progression | 2 | 0 | 1 | 0 | 0 |
| Randomized Part | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Randomized Part | Sponsor Terminated Study | 0 | 0 | 0 | 19 | 13 |
| Randomized Part | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Paclitaxel Alone in Randomized Part | Total | Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Lapatinib Plus Paclitaxel in Gastrectomy Participants | Lapatinib Plus Paclitaxel in Randomized Part |
|---|---|---|---|---|---|
| Age Continuous | 60.4 Years STANDARD_DEVIATION 10.96 | 60.5 Years STANDARD_DEVIATION 10.23 | 57.5 Years STANDARD_DEVIATION 11.31 | 57.2 Years STANDARD_DEVIATION 10.98 | 60.8 Years STANDARD_DEVIATION 9.45 |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 75 Participants | 148 Participants | 0 Participants | 0 Participants | 73 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 48 Participants | 112 Participants | 6 Participants | 6 Participants | 52 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 6 Participants | 13 Participants | 0 Participants | 0 Participants | 7 Participants |
| Sex: Female, Male Female | 23 Participants | 55 Participants | 1 Participants | 0 Participants | 31 Participants |
| Sex: Female, Male Male | 106 Participants | 218 Participants | 5 Participants | 6 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 131 / 131 | 126 / 129 |
| serious Total, serious adverse events | 3 / 6 | 2 / 6 | 38 / 131 | 20 / 129 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study
DLTs consisted of only drug-related toxicities (neurologic and non-neurologic DLTs). A neurologic DLT was defined as grade 3/4 clinically significant peripheral motor and/or sensitive neuropathy. Non-neurologic DLTs mainly included the following: grade 3/4 clinically significant non-hematological toxicity (except nausea), grade 4 neutropenia lasting \>=7 days, thrombocytopenia (\<=25000 cells per cubic millimeter), inability to begin next treatment within 2 weeks of scheduled dosing due to unresolved toxicity, treatment delay (due to toxicity) of \>5 days, for Days 8 or 15 of weekly paclitaxel.
Time frame: 28 days
Population: Safety Population (Pilot part): all participants who received at least one dose of investigational product in the Pilot part of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study | 2 Participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With Dose Limiting Toxicities (DLTs) in the Pilot Part of the Study | 1 Participants |
Primary
Overall Survival (OS) in the Randomized Part of the Study
OS was defined as the time from randomization until death due to any cause. For participants who did not die, time to death was censored at the time of last contact. For censored participants, time to death was defined as the time from randomization to the time of last contact.
Time frame: From randomization until death due to any cause (up to 42.58 months)
Population: Intent-to-Treat Population: all participants who were randomized to study treatment, regardless of whether they actually received study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Overall Survival (OS) in the Randomized Part of the Study | 11.0 months |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Overall Survival (OS) in the Randomized Part of the Study | 8.9 months |
p-value: 0.208895% CI: [0.64, 1.11]Log Rank
Secondary
Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study
PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14. AUC is defined as the area under the lapatinib concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from time 0 to 24 hours after oral adminisation.
Time frame: Days 8 and 14
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study | Day 8 | 86584.045 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study | Day 14 | 68177.402 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study | Day 8 | 37332.880 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lapatinib in the Pilot Part of the Study | Day 14 | 30565.248 hr*ng/mL |
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study
PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-inf) is area under the plasma concentration-time curve from the start of infusion (time 0) extrapolated to infinity.
Time frame: Days 1 and 8
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study | Day 1 | 6262.157 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study | Day 8 | 8340.326 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study | Day 1 | 4058.648 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Paclitaxel in the Pilot Part of the Study | Day 8 | 6020.878 hr*ng/mL |
Secondary
AUC(0-24) of Paclitaxel in the Pilot Part of the Study
PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. AUC is defined as the area under the paclitaxel concentration-time curve as a measure of drug exposure. AUC(0-24) is area under the plasma concentration-time curve from the start of infusion (time 0) to 24 hours after the start of the infusion.
Time frame: Days 1 and 8
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | AUC(0-24) of Paclitaxel in the Pilot Part of the Study | Day 1 | 5771.847 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | AUC(0-24) of Paclitaxel in the Pilot Part of the Study | Day 8 | 7492.825 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | AUC(0-24) of Paclitaxel in the Pilot Part of the Study | Day 1 | 3968.654 hr*ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | AUC(0-24) of Paclitaxel in the Pilot Part of the Study | Day 8 | 4992.934 hr*ng/mL |
Secondary
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study | 12.59 scores on a scale | Standard Deviation 28.521 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Appetite Loss Symptom Score at the End of Therapy in the Randomized Part of the Study | 7.04 scores on a scale | Standard Deviation 28.683 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study | -10.19 scores on a scale | Standard Deviation 16.133 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Score at the End of Therapy in the Randomized Part of the Study | -12.14 scores on a scale | Standard Deviation 20.446 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study | 5.93 scores on a scale | Standard Deviation 27.176 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Constipation Symptom Score at the End of Therapy in the Randomized Part of the Study | 2.35 scores on a scale | Standard Deviation 26.621 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study | 10.00 scores on a scale | Standard Deviation 31.385 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Diarrhea Symptom Score at the End of Therapy in the Randomized Part of the Study | 4.29 scores on a scale | Standard Deviation 24.025 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study | 12.22 scores on a scale | Standard Deviation 22.037 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Dyspnea Symptom Score at the End of Therapy in the Randomized Part of the Study | 15.02 scores on a scale | Standard Deviation 23.764 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study | -10.65 scores on a scale | Standard Deviation 19.594 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Score at the End of Therapy in the Randomized Part of the Study | -10.12 scores on a scale | Standard Deviation 22.066 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study | 11.98 scores on a scale | Standard Deviation 21.084 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Fatigue Symptom Score at the End of Therapy in the Randomized Part of the Study | 14.79 scores on a scale | Standard Deviation 23.885 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study | 7.04 scores on a scale | Standard Deviation 28.042 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Symptom Score at the End of Therapy in the Randomized Part of the Study | 0.95 scores on a scale | Standard Deviation 27.2 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study | 5.56 scores on a scale | Standard Deviation 28.813 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Insomnia Symptom Score at the End of Therapy in the Randomized Part of the Study | 10.80 scores on a scale | Standard Deviation 27.473 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Symptom Score at the End of Therapy in the Randomized Part of the Study | 4.26 scores on a scale | Standard Deviation 17.411 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Symptom Score at the End of Therapy in the Randomized Part of the Study | 7.28 scores on a scale | Standard Deviation 19.666 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study | 7.41 scores on a scale | Standard Deviation 27.038 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Pain Symptom Score at the End of Therapy in the Randomized Part of the Study | 12.68 scores on a scale | Standard Deviation 29.743 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study | -13.48 scores on a scale | Standard Deviation 18.776 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Score at the End of Therapy in the Randomized Part of the Study | -13.99 scores on a scale | Standard Deviation 21.087 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study | -17.41 scores on a scale | Standard Deviation 24.468 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Role Functioning Score at the End of Therapy in the Randomized Part of the Study | -18.31 scores on a scale | Standard Deviation 27.625 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study | -10.74 scores on a scale | Standard Deviation 26.122 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-C30 Social Functioning Score at the End of Therapy in the Randomized Part of the Study | -13.33 scores on a scale | Standard Deviation 22.089 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study | 8.27 scores on a scale | Standard Deviation 24.624 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Anxiety Scale Score at the End of Therapy in the Randomized Part of the Study | 2.97 scores on a scale | Standard Deviation 21.899 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study | 15.99 scores on a scale | Standard Deviation 27.442 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Body Image Scale Score at the End of Therapy in the Randomized Part of the Study | 8.45 scores on a scale | Standard Deviation 32.229 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study | 8.15 scores on a scale | Standard Deviation 27.053 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Dry Mouth Scale Score at the End of Therapy in the Randomized Part of the Study | 2.35 scores on a scale | Standard Deviation 21.324 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study | 10.37 scores on a scale | Standard Deviation 21.382 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Dysphagia Scale Score at the End of Therapy in the Randomized Part of the Study | 5.16 scores on a scale | Standard Deviation 14.887 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study | 8.33 scores on a scale | Standard Deviation 18.78 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Eating Restrictions Scale Score at the End of Therapy in the Randomized Part of the Study | 6.69 scores on a scale | Standard Deviation 18.72 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study | 9.09 scores on a scale | Standard Deviation 31.171 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Hair Loss Scale Score at the End of Therapy in the Randomized Part of the Study | 7.69 scores on a scale | Standard Deviation 33.758 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study | 5.46 scores on a scale | Standard Deviation 16.151 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Pain Scale Score at the End of Therapy in the Randomized Part of the Study | 3.40 scores on a scale | Standard Deviation 14.542 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study | 3.33 scores on a scale | Standard Deviation 14.177 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Reflux Symptoms Scale Score at the End of Therapy in the Randomized Part of the Study | 2.66 scores on a scale | Standard Deviation 15.312 |
Secondary
Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-STO22 is a 22-item, self-reporting instrument consisting of 5 scales and 4 single items to assess health-related quality of life (HRQOL) issues related to dysphagia, eating restrictions, reflux, and abdominal pain, as well as specific symptoms that may occur during chemotherapy or radiation treatment. Scores are averaged and transformed to a 0-100 scale. For the symptom scales and items, a high score is equivalent to worse or more symptoms. In the functional scales, however, a high score is equivalent to better function.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study | 13.70 scores on a scale | Standard Deviation 28.659 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the EORTC QLQ-STO22 Taste Scale Score at the End of Therapy in the Randomized Part of the Study | 3.29 scores on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QOL Score at the End of Therapy in the Randomized Part of the Study
The EORTC QLQ-C30 is a 30-item, self-reporting questionnaire assessing 15 domains (5 functional scales \[physical/role/emotional/cognitive/social\]; 9 symptom scales \[fatigue/nausea and vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea/financial difficulties\]; GHS/QOL scale). Participants assessed most statements on a 4-point scale (1, not at all; 4, very much); two questions used a 7-item scale (1, poor; 7, excellent). Scores were averaged and transformed to a 0-100 scale. A high score indicates both a high/healthy level of functioning and a high level of symptoms/problems.
Time frame: Baseline and end of therapy (up to 42.58 months)
Population: ITT Population. Only those participants who contributed data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QOL Score at the End of Therapy in the Randomized Part of the Study | -12.41 scores on a scale | Standard Deviation 25.578 |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QOL Score at the End of Therapy in the Randomized Part of the Study | -11.55 scores on a scale | Standard Deviation 28.562 |
Secondary
Clearance of Paclitaxel in the Pilot Part of the Study
PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Clearance is defined as the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.
Time frame: Days 1 and 8
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Clearance of Paclitaxel in the Pilot Part of the Study | Day 1 | 12.775 liters per hour per square meter |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Clearance of Paclitaxel in the Pilot Part of the Study | Day 8 | 9.592 liters per hour per square meter |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Clearance of Paclitaxel in the Pilot Part of the Study | Day 1 | 17.744 liters per hour per square meter |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Clearance of Paclitaxel in the Pilot Part of the Study | Day 8 | 13.287 liters per hour per square meter |
Secondary
Cmax of Paclitaxel in the Pilot Part of the Study
PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8.
Time frame: Days 1 and 8
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Cmax of Paclitaxel in the Pilot Part of the Study | Day 1 | 4121.513 ng/mL |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Cmax of Paclitaxel in the Pilot Part of the Study | Day 8 | 4610.176 ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Cmax of Paclitaxel in the Pilot Part of the Study | Day 1 | 2731.104 ng/mL |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Cmax of Paclitaxel in the Pilot Part of the Study | Day 8 | 2949.770 ng/mL |
Secondary
Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study
PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Vss is the volume of distribution at steady state of paclitaxel.
Time frame: Days 1 and 8
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study | Day 1 | 76.011 liters per square meter |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study | Day 8 | 71.223 liters per square meter |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study | Day 1 | 141.196 liters per square meter |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Distribution Volume at Steady State (Vss) of Paclitaxel in the Pilot Part of the Study | Day 8 | 126.121 liters per square meter |
Secondary
Duration of Response in the Randomized Part of the Study
Duration of response was defined as the time from the first documented evidence of CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD) until the first documented sign of disease progression (at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions) or death due to any cause, if sooner.
Time frame: up to 18.27 months
Population: ITT Population. Only those participants achieving a CR or PR were assessed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Duration of Response in the Randomized Part of the Study | 7.4 months |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Duration of Response in the Randomized Part of the Study | 5.1 months |
Secondary
Half-life of Paclitaxel in the Pilot Part of the Study
PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8. Half-life is defined as the time required for the amount of the drug in the plasma to decrease by half.
Time frame: Days 1 and 8
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Half-life of Paclitaxel in the Pilot Part of the Study | Day 1 | 10.128 hr |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Half-life of Paclitaxel in the Pilot Part of the Study | Day 8 | 10.342 hr |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Half-life of Paclitaxel in the Pilot Part of the Study | Day 1 | 13.053 hr |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Half-life of Paclitaxel in the Pilot Part of the Study | Day 8 | 13.978 hr |
Secondary
Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study
Pharmacokinetic (PK) samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14.
Time frame: Days 8 and 14
Population: PK Parameter Population: all participants for whom the PK parameter could be estimated
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study | Day 8 | 5435.525 nanograms per milliliter (ng/mL) |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study | Day 14 | 3930.780 nanograms per milliliter (ng/mL) |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study | Day 8 | 3129.561 nanograms per milliliter (ng/mL) |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Maximum Plasma Concentration (Cmax) of Lapatinib in the Pilot Part of the Study | Day 14 | 2062.557 nanograms per milliliter (ng/mL) |
Secondary
Number of Participants With Mutations That May Correlate With Response and Toxicity to Lapatinib
An inadequate number of tissue samples were obtained; thus, analysis could not be performed.
Time frame: Pretreatment
Population: ITT Population
Secondary
Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study
EGFR protein expression on the surface of cells in gastric cancer tissue samples was measured using a moncolonal antibody specific for the extracellular region of EGFR, and the degree of membrane staining was evaluated. 3+ indicates positive EGFR expression; \<3+ indicates negative EGFR expression.
Time frame: Pretreatment
Population: ITT Population. Only those participants for whom immunohistochemistry testing was conducted were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study | <3+ | 68 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study | 3+ | 5 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study | <3+ | 59 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Epidermal Growth Factor Receptor (EGFR) Immunohistochemistry Intensity in the Randomized Part of the Study | 3+ | 6 participants |
Secondary
Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study
The Common Terminology Criteria for Advere Events (CTCAE) is a descriptive terminology that can be used for AE reporting. Grade (G) refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade (G) refers to the severity of the AE: G 1, mild AE; G 2, moderate AE; G 3, severe AE; G 4, life-threatening/disabling AE; G 5, death related to the AE.
Time frame: From the first dose of investigational product to 30 days after the last dose (up to 110.3 weeks in the Randomized part)
Population: Safety Population: all participants who were randomized and took at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Nausea, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pyrexia, Grade 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Leukopenia, Grade 3 | 32 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pyrexia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Stomatitis, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Asthenia, Grade 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Leukopenia, Grade 4 | 7 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Asthenia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Diarrhoea, Grade 3 | 23 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Weight decreased, Grade 3 | 2 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Anaemia, Grade 3 | 10 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Weight decreased, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Constipation, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | White blood cell count decreased, Grade 3 | 18 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Anaemia, Grade 4 | 4 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | White blood cell count decreased, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Vomiting, Grade 3 | 4 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutrophil count decreased, Grade 3 | 11 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Lymphopenia, Grade 3 | 4 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutrophil count decreased, Grade 4 | 5 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Constipation, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Lymphopenia, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Haemoglobin decreased, Grade (G) 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Nausea, Grade 3 | 5 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Aspartate aminotransferase increased, G 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alopecia, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Aspartate aminotransferase increased, G 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Abdominal pain, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alanine aminotransferase increased, G 3 | 2 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alopecia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alanine aminotransferase increased, G 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Vomiting, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Peripheral sensory neuropathy, G 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Rash, Grade 3 | 3 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Peripheral sensory neuropathy, G 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Abdominal pain, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neuropathy peripheral, Grade 3 | 2 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Rash, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neuropathy peripheral, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Diarrhoea, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Decreased appetite, Grade 3 | 11 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pruritus, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Decreased appetite, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutropenia, Grade 3 | 41 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Myalgia, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pruritus, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Myalgia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Stomatitis, Grade 3 | 2 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Arthralgia, Grade 3 | 2 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Fatigue, Grade 3 | 6 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Arthralgia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutropenia, Grade 4 | 34 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Back pain, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Fatigue, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Back pain, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Haemoglobin decreased, Grade 3 | 9 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Back pain, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Diarrhoea, Grade 3 | 3 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Diarrhoea, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Nausea, Grade 3 | 3 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Nausea, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Vomiting, Grade 3 | 4 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Vomiting, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Stomatitis, Grade 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Stomatitis, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Constipation, Grade 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Constipation, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Abdominal pain, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Abdominal pain, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutropenia, Grade 3 | 33 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutropenia, Grade 4 | 6 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Leukopenia, Grade 3 | 12 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Leukopenia, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Anaemia, Grade 3 | 8 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Anaemia, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Lymphopenia, Grade 3 | 2 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Lymphopenia, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alopecia, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alopecia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Rash, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Rash, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pruritus, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pruritus, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Fatigue, Grade 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Fatigue, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pyrexia, Grade 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Pyrexia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Asthenia, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Asthenia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Weight decreased, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Weight decreased, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | White blood cell count decreased, Grade 3 | 6 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | White blood cell count decreased, Grade 4 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutrophil count decreased, Grade 3 | 4 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neutrophil count decreased, Grade 4 | 2 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Haemoglobin decreased, Grade 3 | 5 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Haemoglobin decreased, Grade (G) 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Aspartate aminotransferase increased, G 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Aspartate aminotransferase increased, G 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alanine aminotransferase increased, G 3 | 2 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Alanine aminotransferase increased, G 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Peripheral sensory neuropathy, G 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Peripheral sensory neuropathy, G 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neuropathy peripheral, Grade 3 | 1 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Neuropathy peripheral, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Decreased appetite, Grade 3 | 9 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Decreased appetite, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Myalgia, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Myalgia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Arthralgia, Grade 3 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Arthralgia, Grade 4 | 0 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Grade 3 and Grade 4 Adverse Events (AEs) for Which All Grades of the AE Were Reported in >=10% of Participants, Regardless of Causality in the Randomized Part of the Study | Back pain, Grade 3 | 0 participants |
Secondary
Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study
HER2 protein expression on the surface of cells in gastric cancer tissue samples was measured using a monoclonal antibody specific for the extracellulr region of HER2, and the degree of membrane staining was evaulated. The immunohistochemistry test gives a score of 0 to 3+ and measures the amount of HER2 receptor protein on the surface of cells in a gastric cancer tissue sample. Score of 0 to 1+, HER2 negative; score of 2+, borderline; score of 3+, HER2 positive.
Time frame: Pretreatment
Population: ITT Population. Only those participants for whom immunohistochemistry testing was conducted were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study | 0/1+ | 36 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study | 2+ | 12 participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study | 3+ | 52 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study | 0/1+ | 32 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study | 2+ | 11 participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry Intensity in the Randomized Part of the Study | 3+ | 49 participants |
Secondary
Number of Participants With the Indicated Time to Response in the Randomized Part of the Study
Time to response was defined as the time from randomization to CR (the disappearance of all target lesions) or PR (a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD). For participants who did not achieve a CR or PR, time to response was censored at the last assessment prior to other cancer therapies. For censored participants, time to response was defined as the time from randomization to the time of the last assessment prior to the administation of other cancer therapies.
Time frame: up to 5.62 months
Population: ITT Population. Only those participants achieving a CR or PR were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks 1-8 | 13 Participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks >8 - 16 | 20 Participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks >16 - 24 | 1 Participants |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks >24 - 32 | 1 Participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks >24 - 32 | 0 Participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks 1-8 | 5 Participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks >16 - 24 | 3 Participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Number of Participants With the Indicated Time to Response in the Randomized Part of the Study | Weeks >8 - 16 | 3 Participants |
Secondary
Percentage of Participants With Overall Response in the Randomized Part of the Study
Overall response was defined as the percentage of participants achieving either complete response (CR) or partial response (PR). Per RECIST, version 1.0, CR was defined as the disappearance of all target lesions, and PR was defined as a greater than 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Time frame: From randomization up to 5.62 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Percentage of Participants With Overall Response in the Randomized Part of the Study | 27 Percentage of participants |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Percentage of Participants With Overall Response in the Randomized Part of the Study | 9 Percentage of participants |
Secondary
Progression-free Survival (PFS) in the Randomized Part of the Study
PFS was defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
Time frame: From randomization until disease progression or death due to any cause (up to 42.35 months)
Population: ITT Population. For participants whose disease did not progress or who did not die, PFS was censored at the time of the last independently assessed radiological scan preceding the initiation of any alternate anti-cancer therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Progression-free Survival (PFS) in the Randomized Part of the Study | 5.4 months |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Progression-free Survival (PFS) in the Randomized Part of the Study | 4.4 months |
Secondary
Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study
PK samples were collected at pre-dose and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 8 and 14.
Time frame: Days 8 and 14
Population: PK Parameter Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study | Day 8 | 4.083 hours (hr) |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study | Day 14 | 7.992 hours (hr) |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study | Day 8 | 3.500 hours (hr) |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Time to Cmax (Tmax) of Lapatinib in the Pilot Part of the Study | Day 14 | 4.000 hours (hr) |
Secondary
Time to Progression in the Randomized Part of the Study
Time to progression was defined as the time from randomization until the earliest date of disease progression or death due to disease. Per RECIST, version 1.0, PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
Time frame: From randomization until disease progression or death due to disease (up to 42.35 months )
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Time to Progression in the Randomized Part of the Study | 5.5 months |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Time to Progression in the Randomized Part of the Study | 4.4 months |
Secondary
Tmax of Paclitaxel in the Pilot Part of the Study
PK samples were collected just before the start of infusion and 0.5, 1.0 (immediately before terminating the infusion), 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Days 1 and 8.
Time frame: Days 1 and 8
Population: PK Parameter Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Tmax of Paclitaxel in the Pilot Part of the Study | Day 1 | 1.042 hr |
| Lapatinib Plus Paclitaxel in Non-gastrectomy Participants | Tmax of Paclitaxel in the Pilot Part of the Study | Day 8 | 1.050 hr |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Tmax of Paclitaxel in the Pilot Part of the Study | Day 1 | 1.075 hr |
| Lapatinib Plus Paclitaxel in Gastrectomy Participants | Tmax of Paclitaxel in the Pilot Part of the Study | Day 8 | 1.025 hr |