Tykerb Evaluation After Chemotherapy (TEACH): Lapatinib V... | NCT00374322

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	6 tablets daily for 12 months	Other: placebo
Lapatinib	Experimental	Lapatinib 1500 mg (6 tablets) daily for 12 months	Drug: lapatinib

Name	Type	Description	Arm Group Labels	Other Names
lapatinib	Drug	Lapatinib 1500 mg (6 tablets) daily for 12 months	Lapatinib

Measure	Description	Time Frame
Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ; other second primary cancer (excluding squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast); death from any cause without a prior event. Par. who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Par. who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.	From randomization until date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause (assessed up to 6 years; 1 year of treatment, 5 years of follow-up [median of 5.3 years for final analysis])

Measure	Description	Time Frame
Number of Participants Who Died (Overall Survival)	Overall Survival (OS) is defined as the time from randomization until death from any cause. Data are presented as the number of participants who died. For participants who did not die, time to death was censored at the last date the participant was known to be alive.	From the date of randomization until death from any cause (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have histologically or cytologically confirmed ErbB2-overexpressing invasive carcinoma (TX or T1-4) of the breast at the time of the initial diagnosis and have undergone adequate excision of tumor;
Had tumors that overexpress ErbB2 defined as 3+ by IHC or c-erbB2 gene amplification by FISH (ErbB2 expression/amplification must be documented prior to study entry; however, a tumor tissue sample must be sent to a central laboratory for subsequent re-analysis of ErbB2 status);
Have Stage I through Stage IIIc disease according to the American Joint Committee on Cancer (6th edition) staging criteria for breast cancer and meet one of the following criteria:

node-positive disease defined as: one positive lymph node by sentinel node biopsy OR at least 1 positive lymph node found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN1 or cN2 (if sentinel node biopsy is positive, subject may either undergo an axillary node dissection or radiotherapy to the axilla).

node-positive disease evaluated as: ipsilateral axillary lymph nodes cN0-2 by clinical evaluation and axillary lymph nodes pNX, pN0(i+), or pN1-3 by pathological evaluation [patients with pN3 (Stage IIIc disease) must be disease free following completion of neoadjuvant or adjuvant chemotherapy for at least 12 months and must not have been lost to follow up].

OR node-negative disease defined as: negative sentinel node biopsy OR no positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN0.

node-negative disease categorized as: high-risk disease (tumor >2.0 cm if ER and/or progesterone receptor (PgR) positive disease is present or tumor >1.0 cm if ER and PgR negative disease) OR intermediate-risk disease (tumor 1.0-2.0 cm and ER and/or PgR positive disease).

Women with synchronous bilateral invasive breast cancer or synchronous DCIS of either the contralateral or ipsilateral breast at the time of the initial diagnosis are also eligible;
Have undergone either mastectomy OR lumpectomy;
Have received and completed treatment with a neoadjuvant or adjuvant chemotherapy regimen containing either an anthracycline or a taxane; or any cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen;
May continue to receive endocrine therapy while taking study medication, if endocrine therapy was initiated as either adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer or for ovarian function suppression; however, endocrine therapy may not be initiated while taking study medication. Endocrine therapy agents may be switched while participating in this study (e.g., stop tamoxifen and start letrozole);
May have received prior radiotherapy as treatment for primary tumor; however, is not required for study entry;
May continue to receive radiotherapy while taking study medication, if radiotherapy was initiated as adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer;
May continue to receive bisphosphonates only for treatment of documented osteoporosis, but not as treatment or prophylaxis of bone metastases;
All women eligible for adjuvant treatment with trastuzumab, including those diagnosed and treated within the last six months, must be considered for such treatment prior to being offered participation in this study. Participation in this study will be allowed only if the physician and patient have considered and discussed at length the advantages of trastuzumab, but have mutually decided against initiating trastuzumab therapy.
Have clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry;
if signs or symptoms suggestive of either recurrence of disease or metastatic disease are present, the appropriate radiological imaging must be performed
if the following laboratory results are present, the appropriate radiological imaging must be performed:
for AST/ALT ≥2×ULN or ALP ≥2×ULN (not in the bone fraction), an abdominal CT or MRI must be done
for ALP≥2×ULN in the bone fraction, a bone scan must be done; a confirmatory x-ray, CT scan or MRI scan or biopsy is required if the results of the bone scan are inconclusive
Have a unilateral/bilateral mammogram within 12 months prior to study entry;
Have an analysis of both ER and PgR on the primary tumor prior to study entry;
Have a cardiac ejection fraction within institutional range of normal as measured by either echocardiogram or multigated acquisition scans;
Have an Eastern Cooperative Oncology Group Performance Status of 0 to 1;
Women with a history of non-breast malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence. Women with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical carcinoma in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin;
Are able to swallow and retain oral medication;
Have a paraffin-embedded tissue block from an archived tumor tissue from the primary tumor or twenty (20) slides of paraffin-embedded tissue available for biomarker analysis;
Have adequate organ function defined as: absolute neutrophil count ≥1.5× 10^9/L; hemoglobin ≥9 g/dL; platelets ≥75 × 10^9/L; albumin ≥2.5 g/dL; serum bilirubin ≤1.25 ×ULN; aspartate aminotransferase and alanine aminotransferase ≤3 × ULN and serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥40 mL/min
Have signed the informed consent form (ICF);
Women of child-bearing potential must have a negative serum pregnancy test at screening and agree to complete abstinence from intercourse or consistent and correct use of an acceptable methods of birth control from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication:

Exclusion Criteria:

Have clinical and radiologic evidence of local or regional recurrence of disease or metastatic disease at the time of study entry;
Had metachronous invasive breast cancer (breast cancers diagnosed at different times);
Have a prior history of other breast cancer malignancies, including DCIS;
Are unable to provide archived tumor tissue samples for assay;
Had prior therapy with an ErbB1 and/or ErbB2 inhibitor; women who experienced a hypersensitivity or allergic reaction to trastuzumab during the first infusion and were unable to complete this infusion are eligible;
Receive concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication;
Have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded;
Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety;
Have an active or uncontrolled infection;
Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
Have a known history of uncontrolled or symptomatic angina, arrhythmias, or CHF;
Are pregnant or breastfeeding;
Receive concurrent treatment with an investigational agent; women, who are in follow-up in another clinical trial where the primary endpoint has been met and the interval between assessments is ≥12 months and radiological imaging is not required at these assessments, are eligible;
Receive concurrent treatment with a selected list of strong inducers and inhibitors of CYP3A4;
Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication;
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients;

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Tuscaloosa	Alabama	35406	United States
GSK Investigational Site

PubMed Identifier	Type	Citation
	Background	P Goss, I Smith, J O'Shaughnessy, B Ejlertsen, M Kaufmann, F Boyle, A Buzdar, P Fumoleau, W Gradishar, M Martin, B Moy, M Piccart-Gebhart, K I Pritchard, D Lindquist, Y Chavarri-Guerra, G Aktan, E Rappold, L S Williams, D M Finkelstein. Resubmission: A Randomized Trial of Adjuvant Lapatinib in Women with Early Stage HER2 Overexpressing Breast Cancer. Lancet Oncol. 2012;S 1470-2045(12):70508-9.
25752740	Derived	Boyle FM, Smith IE, O'Shaughnessy J, Ejlertsen B, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard KI, Lindquist D, Amonkar M, Huang Y, Rappold E, Williams LS, Wang-Silvanto J, Kaneko T, Finkelstein DM, Goss PE; TEACH Investigators. Health related quality of life of women in TEACH, a randomised placebo controlled adjuvant trial of lapatinib in early stage Human Epidermal Growth Factor Receptor (HER2) overexpressing breast cancer. Eur J Cancer. 2015 Apr;51(6):685-96. doi: 10.1016/j.ejca.2015.02.005. Epub 2015 Mar 6.
24687830

ID	Title	Description
FG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])

DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ; other second primary cancer (excluding squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast); death from any cause without a prior event. Par. who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Par. who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.

Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of randomized treatment (lapatinib or placebo). Data for the end-of-study analysis (conducted in 2013) are reported.

Posted

Number

Participants

From randomization until date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause (assessed up to 6 years; 1 year of treatment, 5 years of follow-up [median of 5.3 years for final analysis])

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Units	Counts
Participants	OG0001571 OG0011576

Title

Denominators

Categories

Any recurrence or death

Title	Measurements
	OG000252 OG001290

Censored, New Anti-cancer Agent/Radiotherapy

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.286	The p-value was calculated from a stratified log-rank test, stratifying for hormone receptor status, time since initial diagnosis, and lymph node involvement.	Hazard Ratio (HR)	0.91			2-Sided	95	0.77	1.08			Estimate of the treatment hazard ratio (HR) was calcuated using the pike estimator.	No	Superiority or Other

Secondary

Number of Participants Who Died (Overall Survival)

Overall Survival (OS) is defined as the time from randomization until death from any cause. Data are presented as the number of participants who died. For participants who did not die, time to death was censored at the last date the participant was known to be alive.

ITT Population. Data for the primary analysis (conducted in 2011) are reported.

Posted

Number

Participants

From the date of randomization until death from any cause (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)

Recurrence is defined as experiencing a recurrence of initial disease or contralateral breast cancer after randomization. Time to first recurrence is defined as the interval between the date of randomization and the date of the first occurrence of an objective disease recurrence or contralateral breast cancer. Time to first recurrence included the first occurrence at one of the following sites as an event: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ (DCIS).

ITT Population. Data for the primary analysis (conducted in 2011) are reported.

Posted

Number

Percentage of participants

From the date of randomization until the date of the first occurrence of an objective disease recurrence or contralateral breast cancer (assessed up to 6 years; 1 year of treatment and 5.3 years of follow-up [median of 5 years for final analysis])

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)

Distant recurrence (metastatic disease) is defined as a tumor in any area of the body not including those defined as local or regional recurrence. Sites of distant recurrence include: skin, subcutaneous tissue, and lymph nodes (excluding those described for local and regional recurrence); bone marrow; skeletal; lungs and pleural; ascites and pleural effusions; liver and other viscera; and central nervous system (CNS). Time to distant recurrence is defined as the interval between the date of randomization and the date of the first occurrence of a distant recurrence.

ITT Population. Data for the primary analysis (conducted in 2011) are reported.

Posted

Number

Percentage of participants

From the date of randomization until the date of the first occurrence of a distant recurrence (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Time to Central Nervous System (CNS) Recurrence

Time to CNS recurrence is defined as the interval between the date of randomization and the date of the occurrence of a CNS recurrence if noted as part of the participant's first recurrence. Time to CNS recurrence was not calculated; data are presented as the number of participants with CNS recurrence in the subsequent outcome measure table.

Posted

From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Units	Counts

Secondary

Number of Participants With CNS Recurrence

The number of participants experiencing a CNS recurrence was summarized.

ITT Population. Data for the end-of-study analysis (conducted in 2013) are reported.

Posted

Number

Participants

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Units	Counts
Participants

Secondary

Modified Disease-free Survival (MDFS)

Modified disease recurrence=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause. The date of the event=the earliest date of the occurrence of any of the following events: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including DCIS; death from any cause without a prior event. MDFS was not calculated; data are presented as the number of participants with any recurrence of the initial disease, contralateral breast cancer, or death (disease-free survival) in the subsequent outcome measure table.

Posted

From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Number of Participants With Any Recurrence of the Initial Disease, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])

DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence and contralateral breast cancer, including ductal carcinoma in situ; or death from any cause without a prior event. Participants who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Participants who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.

ITT Population. Data for the end-of-study analysis (conducted in 2013) are reported.

Posted

Number

Participants

From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001

Secondary

Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)

The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The PCS score is a summary score representing overall physical health, which is derived from the 8 domain scores. As with each domain score, the PCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the last observation carried forward (LOCF) method. The scores were analyzed using an analysis of covariance (ANCOVA) model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.

ITT Population (primary analysis [conducted in 2011]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)

The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The MCS score is a summary score representing overall mental health, which is derived from the 8 domain scores. As with each domain score, the MCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.

ITT Population (primary analysis [conducted in 2011]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)

The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH) perceptions, vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). Each domain is scored from 0 (poorer health) to 100 (better health); higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.

ITT Population (primary analysis [conducted in 2011]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Scores on a scale

Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters

The hematology parameters assessed were: basophils (Bs) in giga (10^9) per liter (GI/L) and in percentage (%), eosinophils (Eo) in GI/L and %, hematocrit, hemoglobin, lymphocytes (Lmph) in GI/L and %, monocytes (Mono) in GI/L and %, platelet count, Red Blood Cell (RBC) count, total neutrophil count (TNC) in GI/L and %, and White Blood Cell (WBC) count. The Baseline (BL) value is the last available pre-treatment result recorded. "Any post-Baseline value" was based on results recorded at any scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) is presented for BL and "any post-Baseline" (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.

Safety Population (SP): all randomized participants (par.) who received >=1 dose of randomized treatment. Only those par. available (n=X, X in the category titles) at the specified time points were analyzed. Different par. may have been analyzed for different parameters, so the overall number of par. analyzed reflects everyone in the SP.

Posted

Number

Participants

At Baseline and every 3 months thereafter up to Month 12/Early Withdrawal Visit

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters

The clinical chemistry parameters assessed were: alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), bicarbonate, blood urea nitrogen (BUN), bone alkaline phosphatase (Bone ALP), calcium, chloride, creatinine, creatinine clearance (Cr. Clearance), creatinine clearance estimated (Cr. Clrnc. est.), glucose, potassium, sodium, total bilirubin (Total Bln), total protein, urea, and uric acid. The Baseline (BL) value is the last available pre-treatment result recorded. "Any post-Baseline" value was based on results recorded at scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) was presented for BL and "any post-Baseline" (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm.

Safety Population (primary analysis [conducted in 2011]). Only those participants available (represented as n=X, X in the category titles) at the specified time points were analyzed. Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population.

Posted

Number

Participants

At Baseline and every 6 weeks thereafter up to Month 12/Early Withdrawal Visit

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades

Non-laboratory toxicities are defined as adverse events (AEs). The number of partcipants with any treatment-emergent AE of the indicated toxicity grade are summarized. Toxicity grading was according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life threatening; Grade 5=death. The events that were not given a toxicity grade are categorized as "Not Applicable."

Safety Population. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.

Posted

Number

Participants

From the first dose of study treatment up to 12 months

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Secondary

Number of Participants Experiencing Primary or Secondary Cardiac Events

A cardiac event is classified as a primary cardiac endpoint (PCE) or a secondary cardiac endpoint (SCE). PCE is defined as: cardiac death (cardiac death due to heart failure, myocardial infarction, or arrhythmia;or probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event); severe symptomatic congestive heart failure (CHF) (as per New York Heart Association [NYHA] Class III or IV and an absolute decrease in left ventricular ejection fraction [LVEF] of more than 10 percentage points from Baseline and to a left ventricular ejection fraction [LVEF] value below 50%). SCE is defined as asymptomatic or mildly symptomatic cardiac events (NYHA Class I or II) and a significant decrease in LVEF, defined as an absolute decrease in LVEF of more than 10 percentage points from Baseline and to an LVEF value below 50%.

Safety Population (SP). Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.

Posted

Number

Participants

From the date of randomization up to 12 months

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001

Secondary

Number of Participants With the Indicated Electrocardiogram (ECG) Findings

12-lead ECG measurements were taken at Screening and at study conclusion/withdrawal. The number of participants with normal, abnormal clinically significant (CS), and abnormal not clinically significant (NCS) ECG findings, as classified by the investigator, were summarized. Participants with missing values were categorized as missing. Data for the primary analysis (conducted in 2011) are reported.

SP. Only those participants (par.) available at the specified time points were analyzed. Two par. were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm.

Posted

Number

Participants

Screening and Month 12/Early Withdrawal Visit

ID	Title	Description
OG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
OG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Erysipelas	Infections and infestations	MedDRA	Systematic Assessment	EG0008 affected1,573 at risk EG0010 affected1,574 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected1,573 at risk EG0010 affected1,574 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected1,573 at risk EG0012 affected1,574 at risk
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0011 affected1,574 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0011 affected1,574 at risk
Herpes zoster	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected1,573 at risk EG0010 affected1,574 at risk
Abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Breast abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Breast cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Bronchopneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Cystitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Device related infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Gastroenteritis viral	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Implant site cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Lobar pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Streptococcal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Urosepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Wound infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0012 affected1,574 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0012 affected1,574 at risk
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0002 affected1,573 at risk EG0011 affected1,574 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0012 affected1,574 at risk
Contralataral breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0011 affected1,574 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Benign breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Bladder papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Breast cancer in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Cardiac neoplasm unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Haemangioma of liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Intraductal papilloma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Leiomyosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Ovarian epithelial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Ovarian germ cell teratoma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Pancreatic carcinaom metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Skin cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Uterine leiomyosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0007 affected1,573 at risk EG0010 affected1,574 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected1,573 at risk EG0010 affected1,574 at risk
Enteritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0011 affected1,574 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0012 affected1,574 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0012 affected1,574 at risk
Vomiting	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0012 affected1,574 at risk
Abdominal hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Haematochezia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA	Systematic Assessment	EG0003 affected1,573 at risk EG0011 affected1,574 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0013 affected1,574 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected1,573 at risk EG0010 affected1,574 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Pericardial effusion	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Ejection fraction decreased	Investigations	MedDRA	Systematic Assessment	EG0005 affected1,573 at risk EG0016 affected1,574 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Blood bilirubin abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Transaminases increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0011 affected1,574 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Chest injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Road tracffic accident	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Transplant failure	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0012 affected1,574 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Intervertebral disc compression	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Osteochondrosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Cerebellar infarction	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Cerebral infarction	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0002 affected1,573 at risk EG0010 affected1,574 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Cytolytic hepatitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Hepatitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Hepatitis toxic	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0012 affected1,574 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Breast disorder	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Breast mass	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Menometrorrhagia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Menstrual disorder	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Ovarian enlargement	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0012 affected1,574 at risk
Death	General disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Non-cardiac chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Capillary leak syndrome	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Femoral artery occlusion	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Hypertensive crisis	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0011 affected1,574 at risk
Suicide attempt	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0011 affected1,574 at risk
Suicidal ideation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected1,573 at risk EG0010 affected1,574 at risk
Drug hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Hypersensitivity	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected1,573 at risk EG0010 affected1,574 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected1,573 at risk EG0010 affected1,574 at risk
Thyroiditis subacute	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected1,573 at risk EG0011 affected1,574 at risk

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
BG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lapatinib 1500 mg	Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.			99	1,573	1,443	1,573
EG001	Placebo	Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.			78	1,574	1,175	1,574