Lapatinib In Chemotherapy-Naive Or Metastatic Breast Cancer | NCT00089999

Name	Type	Description	Arm Group Labels	Other Names
Lapatinib	Drug

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)	OR is defined as the number of participants achieving either a confirmed CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST, v 1.0). Best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.	From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator	OR is defined as the number of participants achieving either a confirmed CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST, v 1.0). Best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.	From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD] for at Least 24 Weeks), as Assessed by the IRC and Investigator	Clinical benefit is defined as the numer of participants achieving either a confirmed CR (disappearance of all target lesions (TLs) and non-TLs) or PR (at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD,or complete resolution of TLs and the persistence of one or more non-TLs)or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of 1 or more new TLs or non-TLs and/or unequivocal progressionn of existing non-target lesions], taking as reference, the smallest sum LD since the treatment started) for at least 24 weeks. This was based on confirmed responses from the investigator assessment of clinical benefit.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Hollywood	Florida	33021	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
21456017	Background	Lipton A, Leitzel K, Ali SM, Carney W, Platek G, Steplewski K, Westlund R, Gagnon R, Martin AM, Maltzman J. Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy. Cancer. 2011 Nov 1;117(21):5013-20. doi: 10.1002/cncr.26101. Epub 2011 Mar 31.

ID	Title	Description
FG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 milligram (mg) orally once daily (QD). Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

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 With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)

OR is defined as the number of participants achieving either a confirmed CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST, v 1.0). Best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.

Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of investigational product.

Posted

Number

Participants

From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
OG001	Lapatinib 500 mg BID	Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Units	Counts
Participants	OG00069 OG00169

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

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		Fisher Exact		0.691		Odds Ratio (OR)	0.8			2-Sided	95	0.3	1.9				No	Superiority or Other

Primary

Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator

ITT Population

Posted

Number

Participants

From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Secondary

Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD] for at Least 24 Weeks), as Assessed by the IRC and Investigator

Clinical benefit is defined as the numer of participants achieving either a confirmed CR (disappearance of all target lesions (TLs) and non-TLs) or PR (at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD,or complete resolution of TLs and the persistence of one or more non-TLs)or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [at least a 20% increase in the sum of the LD of target lesions, taking as a reference, the smallest sum LD recorded since the treatment started or the appearance of 1 or more new TLs or non-TLs and/or unequivocal progressionn of existing non-target lesions], taking as reference, the smallest sum LD since the treatment started) for at least 24 weeks. This was based on confirmed responses from the investigator assessment of clinical benefit.

ITT Population

Posted

Number

Percentage of Participants

From the date of the first dose of investigational product until the date of disease progression or death due to breast cancer (up to Study Week 103)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Secondary

Time to Response, as Assessed by the IRC and Investigator

Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.

ITT Population. Only those participants with CR or PR were analyzed (represented by n=X in the category titles). Different participants may have been analyzed by the IRC and the Investigator, so the overall number of participants analyzed reflects everyone in the ITT Population.

Posted

Median

Full Range

Weeks

From the date of the first dose of investigational product until the first documented evidence of a PR or CR (up to Study Week 103)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Secondary

Duration of Response (DoR), as Assessed by the IRC and Investigator

DoR is defined for the subset of par. who had a confirmed CR (disappearance of all target lesions (TLs) and non-TLs) or PR (at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of >= 1 non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. For par. who did not progress or die, DoR was censored on the date of the last radiological scan. If a par.had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.

Posted

Median

Inter-Quartile Range

Weeks

From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Study Week 103)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Secondary

Progression-free Survival, as Assessed by the IRC and Investigator

Progression-free survival is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. Disease progression was based on the IRC's and investigator's assessments of the objective evidence (e.g., radiological scans and medical photographs). For participants who did not progress, or die, progression-free survival was censored at the time of the last IRC assessed radiological scan.

ITT Population

Posted

Median

95% Confidence Interval

Weeks

From the date of the first dose of investigational product until the earlier of the date of disease progression or death due to any cause (up to Study Week 103)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
OG001	Lapatinib 500 mg BID	Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Secondary

Time to Treatment Failure, as Assessed by IRC and Investigator

Time to treatment failure is calculated as the interval between the date of randomization and the occurrence of local tumor progression (including ipsilateral [on the same side] and controlateral breast tumor progression), distant tumor progression, permanent treatment discontinuation (either for the experimental or conventional treatment arm), or death due any cause. For participants who did not progress, die or discontinue early, time to treatment failure was censored at the last scan date.

ITT Population

Posted

Median

95% Confidence Interval

Weeks

From randomization until the first documented sign of disease progression, death due to any cause, or early discontinuation from investigational product (up to Study Week 103)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
OG001	Lapatinib 500 mg BID	Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Secondary

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs.

Safety Population: all randomized participants who received at least one dose of investigational product.

Posted

Number

Participants

From the date of the first dose of investigational product until 30 days after the last dose of investigational product (up to study week 192)

ID	Title	Description
OG000	Lapatinib 1500 mg QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
OG001	Lapatinib 500 mg BID	Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected69 at risk EG0011 affected69 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0013 affected69 at risk
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0011 affected69 at risk
Peritonitis bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0011 affected69 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Ejection fraction decreased	Investigations	MedDRA	Systematic Assessment	EG0002 affected69 at risk EG0012 affected69 at risk
Convulsion	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Facial palsy	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Loss of consciousness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0012 affected69 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Pericardial effusion	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0012 affected69 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Hepatorenal syndrome	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Multiple injuries	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0012 affected69 at risk
Confusional state	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Depressed mood	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0011 affected69 at risk
Thrombophlebitis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0010 affected69 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00030 affected69 at risk EG00134 affected69 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected69 at risk EG0019 affected69 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00011 affected69 at risk EG0018 affected69 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0007 affected69 at risk EG0014 affected69 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected69 at risk EG0015 affected69 at risk
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected69 at risk EG0011 affected69 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00023 affected69 at risk EG00122 affected69 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00015 affected69 at risk EG00118 affected69 at risk
Dry skin	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0003 affected69 at risk EG0017 affected69 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0002 affected69 at risk EG0015 affected69 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0004 affected69 at risk EG0010 affected69 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected69 at risk EG0014 affected69 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00011 affected69 at risk EG0019 affected69 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected69 at risk EG0017 affected69 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0004 affected69 at risk EG0012 affected69 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected69 at risk EG0014 affected69 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0008 affected69 at risk EG00110 affected69 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected69 at risk EG0017 affected69 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected69 at risk EG0015 affected69 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0009 affected69 at risk EG0018 affected69 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected69 at risk EG0017 affected69 at risk
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0006 affected69 at risk EG00110 affected69 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0005 affected69 at risk EG0014 affected69 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0005 affected69 at risk EG0016 affected69 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected69 at risk EG0017 affected69 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0003 affected69 at risk EG0016 affected69 at risk
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected69 at risk EG0016 affected69 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0004 affected69 at risk EG0014 affected69 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0003 affected69 at risk EG0014 affected69 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 QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
BG001	Lapatinib 500 mg BID	Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
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 QD	Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.			15	69	58	69
EG001	Lapatinib 500 mg BID	Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.			18	69	53	69