Trial Outcomes & Findings for Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in ErbB2 (HER2) Positive Metastatic Breast Cancer (NCT NCT00820222)

NCT ID: NCT00820222

Last Updated: 2019-04-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

540 participants

Primary outcome timeframe

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

Results posted on

2019-04-02

Participant Flow

Participant milestones

Participant milestones
Measure	Lapatinib Plus Capecitabine Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine Participants received an intravenous (IV) infusion of trastuzumab 8 mg/kilogram (kg) on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Study STARTED	271	269
Overall Study COMPLETED	95	79
Overall Study NOT COMPLETED	176	190

Reasons for withdrawal

Reasons for withdrawal
Measure	Lapatinib Plus Capecitabine Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine Participants received an intravenous (IV) infusion of trastuzumab 8 mg/kilogram (kg) on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Study Lost to Follow-up	10	9
Overall Study Withdrawal by Subject	19	21
Overall Study Physician Decision	93	88
Overall Study Sponsor Terminated Study	43	65
Overall Study Unkown	11	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lapatinib Plus Capecitabine n=271 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=269 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Total n=540 Participants Total of all reporting groups
Age, Continuous	53.4 Years STANDARD_DEVIATION 10.23 • n=5 Participants	55.8 Years STANDARD_DEVIATION 10.26 • n=7 Participants	54.6 Years STANDARD_DEVIATION 10.30 • n=5 Participants
Sex: Female, Male Female	271 Participants n=5 Participants	269 Participants n=7 Participants	540 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European	266 Participants n=5 Participants	260 Participants n=7 Participants	526 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=251 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=250 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Number of Participants With Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse	8 participants	12 participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=271 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=269 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Progression Free Survival (PFS), as Assessed by the Investigator	6.60 months Interval 5.72 to 8.11	8.05 months Interval 6.14 to 8.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=8 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=12 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Time to First CNS Progression, Defined as the Time From Randomization Until the Date of Documented CNS Progression as the First Site of Relapse	8.2 months Standard Deviation 6.78	6.7 months Standard Deviation 6.94

SECONDARY outcome

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

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=271 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=269 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Survival	22.7 months Interval 19.5 to The upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate the upper limit of the 95% CI.	27.3 months Interval 23.7 to The upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate the upper limit of the 95% CI.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=271 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=269 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Number of Participants With Overall Response (OR), as Assessed by the Investigator CR	8 Participants	12 Participants
Number of Participants With Overall Response (OR), as Assessed by the Investigator PR	65 Participants	73 Participants
Number of Participants With Overall Response (OR), as Assessed by the Investigator Overall Response (CR+PR)	73 Participants	85 Participants

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=271 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=269 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Number of Participants With Clinical Benefit (CB) CR	8 Participants	12 Participants
Number of Participants With Clinical Benefit (CB) PR	65 Participants	73 Participants
Number of Participants With Clinical Benefit (CB) SD >= 24 weeks	39 Participants	33 Participants
Number of Participants With Clinical Benefit (CB) Clinical Benefit (CR + PR + SD >= 24 weeks)	112 Participants	118 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=73 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=85 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Duration of Response	6.2 months Interval 5.3 to 10.6	8.4 months Interval 6.0 to 21.6

SECONDARY outcome

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

Population: M-ITT Population

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=251 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=250 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Number of Participants With CNS Progression at Any Time	17 participants	15 participants

SECONDARY outcome

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

Population: Safety Population

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: ITT Population

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Capecitabine n=270 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=267 Participants Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Palmar-plantar erythrodysaesthesia syndrome	29 Participants	45 Participants
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Diarrhoea	19 Participants	22 Participants
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Aspartate aminotransferase increased	11 Participants	4 Participants
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Neutropenia	9 Participants	18 Participants
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Asthenia	9 Participants	6 Participants
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Fatigue	7 Participants	4 Participants
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Alanine aminotransferase increased	4 Participants	6 Participants
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm Hypokalaemia	3 Participants	11 Participants

Adverse Events

Lapatinib Plus Capecitabine

Serious events: 41 serious events

Other events: 241 other events

Deaths: 12 deaths

Trastuzumab Plus Capecitabine

Serious events: 51 serious events

Other events: 236 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Disclosure Office

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER

Measure	Lapatinib Plus Capecitabine n=270 participants at risk Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.	Trastuzumab Plus Capecitabine n=267 participants at risk Participants received an intravenous (IV) infusion of trastuzumab 8 mg/kilogram (kg) on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m\^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
Blood and lymphatic system disorders Anaemia	8.1% 22/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	10.1% 27/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Blood and lymphatic system disorders Leukopenia	4.1% 11/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	7.9% 21/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Blood and lymphatic system disorders Neutropenia	14.1% 38/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	16.5% 44/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Gastrointestinal disorders Abdominal pain upper	7.8% 21/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	6.0% 16/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Gastrointestinal disorders Diarrhoea	46.3% 125/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	40.1% 107/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Gastrointestinal disorders Dyspepsia	7.8% 21/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	7.1% 19/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Gastrointestinal disorders Nausea	30.4% 82/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	18.7% 50/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Gastrointestinal disorders Stomatitis	5.9% 16/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	8.6% 23/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Gastrointestinal disorders Vomiting	13.0% 35/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	10.1% 27/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
General disorders Asthenia	17.0% 46/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	16.9% 45/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
General disorders Fatigue	9.6% 26/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	12.4% 33/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
General disorders Mucosal inflammation	7.8% 21/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	10.1% 27/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
General disorders Pyrexia	7.0% 19/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	9.4% 25/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Hepatobiliary disorders Hyperbilirubinaemia	13.0% 35/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	9.7% 26/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Investigations Alanine aminotransferase increased	12.6% 34/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	13.1% 35/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Investigations Aspartate aminotransferase increased	12.2% 33/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	11.2% 30/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Investigations Blood alkaline phosphatase increased	6.3% 17/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	4.1% 11/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Investigations Blood bilirubin increased	7.0% 19/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	3.4% 9/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Metabolism and nutrition disorders Decreased appetite	10.4% 28/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	7.9% 21/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Musculoskeletal and connective tissue disorders Back pain	5.9% 16/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	4.9% 13/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Musculoskeletal and connective tissue disorders Pain in extremity	5.2% 14/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	3.4% 9/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Nervous system disorders Headache	5.6% 15/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	6.4% 17/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Respiratory, thoracic and mediastinal disorders Cough	8.1% 22/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	6.0% 16/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.1% 11/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	6.7% 18/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Skin and subcutaneous tissue disorders Dry skin	5.6% 15/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	2.6% 7/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Skin and subcutaneous tissue disorders Nail disorder	7.8% 21/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	4.9% 13/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	52.6% 142/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	59.9% 160/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
Skin and subcutaneous tissue disorders Rash	24.4% 66/270 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)	7.9% 21/267 • From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)