Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in ErbB2 (HER2) Positive Metastatic Breast Cancer

CNS relapse is defined as the appearance of \>=1 enhancing lesion measuring \>=6 millimeters (mm) on T1Weighted (T1W) Magnetic Resonance Imaging (MRI) without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a \<6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.

Time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

Population: Modified Intent-to-Treat (M-ITT) Population: all participants who were randomized to study treatment regardless of whether or not treatment was administered and who had no Baseline CNS metastases per Independent Review Committee (IRC) assessment

Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) until the first documented sign of PD (at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions) or death due to breast cancer. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contact.

Time frame: From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 10 months). Cut-off 11-Jun-2012

Population: ITT Population. Only those participants with CR or PR showing PD or death due to breast cancer were analyzed.

Because the study terminated early, pharmacogenetic and biomarker analyses were not performed.

Time frame: Baseline

Population: ITT Population

CB is defined as the number of participants with evidence of confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) at any time or stable disease (SD, neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD \[defined as at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions\] based on investigator assessment), for at least 24 weeks.

Time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

Population: ITT Population. Only those participants enrolled under protocol amendment 3 were required to have PR or CR confirmation. Those participants enrolled under protocol amendments 1 and 2 were considered to have a confirmed response at the time of the first PR or CR regardless of follow-up scans.

CNS progression was documented by a brain scan and was indicated by the investigator on the follow-up electronic Case Report Form. CNS relapse is defined as the appearance of \>=1 enhancing lesion measuring \>=6 mm on T1W MRI without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease, with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a \<6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.

Time frame: From the time of randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012

Population: M-ITT Population

OR is defined as the number of participants with either a confirmed complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD). CR and PR were assessed per Response Evaluation Criteria in Solid Tumors (RECIST). To be assigned a status of PR or CR, a confirmatory disease assessment was to be performed 28 days (4 weeks) or greater after the criteria for response were first met. In addition, a bone scan must have been obtained to rule out the presence of new bone lesions or progression of existing bone lesions, even if the participant had no bone lesions present at Baseline. If a bone scan was performed at the time of initial response or near the time of response, the bone scan did not need to be repeated.

Time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

Population: ITT Population. Only those participants enrolled under protocol amendment 3 were required to have PR or CR confirmation. Those participants enrolled under protocol amendments 1 and 2 were considered to have a confirmed response at the time of the first PR or CR regardless of follow-up scans.

Qualitative and quantitative toxicities were measured as AEs. See the outcome measure entitled Number of participants with the indicated Grade 3 or Grade 4 Adverse Events (AEs) occurring in \>=2 participants in either treatment arm and the AE module of this results summary for a list of AEs occurring in the study. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Time frame: From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months)

Population: Safety Population

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was related to study drug. AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE.

Time frame: From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months).

Population: Safety Population: all participants in the ITT Population who received at least one dose of investigational product, based on the actual treatment received if this differed from that to which the participant was randomized

Overall survival is defined as the time from randomization until death due to any cause or to the date of censor. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contact.

Time frame: From randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012

Population: ITT Population

PFS is defined as the interval between the date of randomization and the earliest date of progressive disease (PD), or death due to any cause. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions based on investigator assessment of both CNS and non-CNS for response.

Time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012

Population: Intent-to-Treat (ITT) Population: all participants who were randomized to study treatment regardless of whether or not treatment was administered

CNS relapse is defined as the appearance of \>=1 enhancing lesion measuring \>=6 mm on T1W MRI without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a \<6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.

Time frame: From randomization until the date of documented CNS progression (average of 10 months). Cut-off 11-Jun-2012

Population: M-ITT Population. Only those participants who had no Baseline CNS metastases and who had CNS progression by radiographic confirmation (per Response Evaluation Criteria in Solid Tumors, 1.0: a 20% increase in the sum of the longest diameter \[LD\] of target lesions or the appearance of \>=1 new lesions) were included in this analysis.