Paclitaxel With / Without GW572016 (Lapatinib) As First Line Therapy For Women With Advanced Or Metastatic Breast Cancer

• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Neoplasms, Breast
Interventions	Drug: Paclitaxel; Drug: GW572016 (Lapatinib)
Enrollment	580

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 580 participants were enrolled and randomized to treatment; however one participant withdrew from the study before taking any medication. Thus, only 579 participants were included in the Intent-to-Treat Population (comprised of all randomized participants who had received at least one dose of randomized therapy [lapatinib or placebo]).

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description	Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Period Title: Overall Study
Started	291	288
Missing	26 [1]	13 [1]
Completed	5	4
Not Completed	286	284
Reason Not Completed
Withdrawal by Subject	28	21
Lost to Follow-up	25	28
Protocol Violation	0	2
Death	198	215
Other/Unknown	9	5
Missing	26	13
[1] These participants have no completion status information recorded on the case report forms.

Baseline Characteristics

Arm/Group Title		Lapatinib With Paclitaxel	Placebo With Paclitaxel	Total
Arm/Group Description		Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Total of all reporting groups
Overall Number of Baseline Participants		291	288	579
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	291 participants	288 participants	579 participants
		51.3 (10.45)	52.4 (10.98)	51.8 (10.72)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	291 participants	288 participants	579 participants
	Female	291 100.0%	288 100.0%	579 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	291 participants	288 participants	579 participants
White		190	182	372
Black		10	10	20
Asian		30	35	65
American Hispanic		54	53	107
Unknown		7	8	15

Outcome Measures

1. Primary Outcome

Title	Time to Progression as Evaluated by the Investigator
Description	Time to progression (TTP) is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The investigator assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors [RECIST] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the investigator, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.
Time Frame	Randomization until the date of disease progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants who had received at least one dose of randomized therapy (lapatinib or placebo)

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Median (Inter-Quartile Range); Unit of Measure: weeks
	29.0; (13.9 to 46.9)	22.9; (12.0 to 38.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lapatinib With Paclitaxel, Placebo With Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.142
	Comments	P-value from stratified log-rank test, stratifying for stage of disease and site of disease at screening
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio, log
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.05
	Estimation Comments	The estimate of the treatment hazard ratio is based on the log-rank test.

2. Primary Outcome

Title	Time to Progression as Evaluated by the Independent Review Committee (IRC)
Description	Time to progression is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The IRC assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors [RECIST] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the independent reviewer, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.
Time Frame	Randomization until the date of disease progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Median (Inter-Quartile Range); Unit of Measure: weeks
	33.7; (18.7 to 69.1)	26.1; (12.9 to 57.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lapatinib With Paclitaxel, Placebo With Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.094
	Comments	P-value from stratified log-rank test, stratifying for stage of disease and site of disease at screening
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio, log
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.04
	Estimation Comments	The estimate of the treatment hazard ratio was based on the log-rank test.

3. Secondary Outcome

Title	Number of Participants With Tumor Response as Evaluated by the Investigator
Description	The percentage of participants with tumor response is defined as those participants with measurable disease who achieved either a complete response (CR) or partial response (PR). The Response Evaluation Criteria in Solid Tumors (RECIST) was used to evaluate the measurability of tumor lesions, to determine target lesion (TLs) and non-target lesion (NTLs). CR (TLs and NTLs): the disappearance of all TLs and NTLs; PR (for TLs): at least a 30% decrease in the sum of the largest diameter (LD) of TLs, taking as a reference the Baseline sum LD; PR (for NTLs): persistence of one or more lesions.
Time Frame	Randomization until the date of disease progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: participants
CR	14	6
PR	88	67

4. Secondary Outcome

Title	Number of Participants With Tumor Response as Evaluated by the Independent Review Committee
Description	The percentage of participants with tumor response is defined as those participants with measurable disease who achieved either a complete response (CR) or partial response (PR). The RECIST criteria was used to evaluate the measurability of tumor lesions, to determine target lesion (TLs) and non-target lesion (NTLs). CR (TLs and NTLs): the disappearance of all TLs and NTLs; PR (for TLs): at least a 30% decrease in the sum of the largest diameter (LD) of TLs, taking as a reference the Baseline sum LD; PR (for NTLs): persistence of one or more lesions.
Time Frame	Randomization until the date of disease progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: participants
CR	1	1
PR	77	53

5. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator
Description	Percentage of participants. with CB is defined as the percentage of participants with evidence of CR (disappearance of all TLs and NTLs), PR (TLs: a >=30% decrease in the sum of the LD, taking as a reference the Baseline sum LD; NTLs: persistence of >=1 lesion), or stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) for >=6 months based on RECIST criteria. PD for TL: a >=20% increase in the sum of the LD of TLs or the appearance of >=1 new lesion. PD for NTLs: the appearance of >=1 new lesion and/or unequivocal progression of existing NTLs.
Time Frame	Randomization until the date of disease progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: Percentage of participants
	40.5	31.9

6. Secondary Outcome

Title	Number of Participants With a Response of CR or PR by the Indicated Study Week
Description	Time to response (TTR) is defined as the time from randomization until the first documented evidence of CR (disappearance of all TLs and NTLs) or PR (for TLs: a >=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD; for NTLs: the persistence of >=1 lesion) (whichever status was recorded first). TTR data are displayed as the number of participants achieving a CR or PR by the indicated week. The investigator evaluated the TTR, and the analysis was based on responses confirmed at a repeat assessment, with the TTR taken as the first time the response was observed.
Time Frame	Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: participants
Week 6	3	0
Week 12	83	55
Week 18	86	57
Week 24	98	69
Week 30	98	69
Week 36	101	71
Week 42	102	72
Week 48	102	72
Week 54	102	72
Week 60	102	72
Week 66	102	72
Week 72	102	73

7. Secondary Outcome

Title	Duration of Response (DOR)
Description	The investigator evaluated the DOR for the subset of participants who showed a CR (disappearance of all TLs and NTLs) or PR (TLs: a >=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD; NTLs: persistence of >=1 lesion). DOR is defined as the time from the first documented evidence of PR or CR until the first documented sign of PD (TL: a >=20% increase in the sum of the LD of TLs or the appearance of >=1 new lesion; NTL: the appearance of >=1 new lesion and/or unequivocal progression of existing NTLs) or death due to breast cancer, if sooner.
Time Frame	From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants who had a CR or PR were evaluated.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	102	73
Median (Inter-Quartile Range); Unit of Measure: weeks
	28.3; (22.3 to 50.0)	27.1; (18.1 to 46.3)

8. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS is defined as the interval between the date of randomization and the earliest date of progression disease (PD) or death due to any cause, if sooner. For TLs, progressive disease is defined as at least a 20% increase in the sum of the LD of TLs or the appearance of 1 or more new lesions. For NTLs, progressive disease is defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. par., participants.
Time Frame	Randomization until the date of disease progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population. PFS was assessed in par. who died or progressed, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored par. (those without a documented date of disease progression/death due to any cause), the date of the last radiographic assessment was used.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Median (95% Confidence Interval); Unit of Measure: weeks
	25.1; (21.9 to 32.1)	22.6; (21.0 to 25.4)

9. Secondary Outcome

Title	Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)
Description	PFS is defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause, if sooner. Six months PFS is defined as PFS at six months from the time of randomization. Raw data for 6 months PFS are not available; thus, data are presented as the number of participants who progressed or died at or prior to 6 months. For TLs, progressive disease is defined asat least a 20% increase in the sum of the LD of TLs or the appearance of 1 or more new lesions. For NTLs, progressive disease is defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. PFS was assessed in participants who died or progressed, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.
Time Frame	Randomization until the date of disease progression or death (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: participants
	133	153

10. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from randomization until death due to any cause.
Time Frame	Randomization until the date of death due to any cause (average of 24 months)

Outcome Measure Data

Analysis Population Description

ITT population. Overall survival was assessed in participants who died as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those still alive), the date of the last contact was used.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Median (95% Confidence Interval); Unit of Measure: months
	23.82; (19.88 to 26.18)	20.17; (17.84 to 23.92)

11. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores
Description	The FACT-B questionnaire was designed to measure multidimensional quality of life (QOL) in participants with breast cancer. The physical and functional well-being subscale scores range from 0 to 28, based on 7 questions (each scored from 0 [not at all] to 4 [very much] for all subscales); the emotional and social/family well-being (1 question optional) subscale scores range from 0 to 24 (based on 6 questions), and the additional concerns subscale score ranges from 0 to 40, based on 10 questions. The FACT-B Total Score (0 [better QOL] to 144 [worse QOL]) is the sum of the subscale scores.
Time Frame	Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants contributing data at the indicated time points were analyzed. Only observed data were collected, and score analyses were conducted using the last observation carried forward (LOCF) method: the last available on-therapy observation for a participant was used to estimate missing data points.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	208	230
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Week 9, n=208, 230	-1.1 (16.09)	-2.3 (16.27)
Week 21, n=126, 125	1.0 (16.63)	-1.3 (17.13)
Week 33, n=72, 64	1.4 (17.39)	-2.0 (12.75)
Week 45, n=35, 38	2.3 (22.05)	-1.4 (10.79)
Withdrawal, n=190, 212	-5.0 (19.53)	-8.4 (17.99)

12. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
Description	The FACT-G questionnaire was designed to measure multidimensional QOL in participants with cancer and includes subscales for physical, social/family, emotional, and functional well-being. The physical, social/family, and functional well-being subscale scores range from 0 to 28, based on responses to 7 questions (each question scored from 0 [not at all] to 4 [very much]); the emotional well-being subscale score ranges from 0 to 24, based on responses to 6 questions. The FACT-G Total Score (ranging from 0 [better QOL] to 108 [worse QOL]) is the sum of the subscale scores.
Time Frame	Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants contributing data at the indicated time points were analyzed. Only observed data were collected, and score analyses were conducted using the LOCF method.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	213	232
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Week 9, n=213, 232	-0.7 (13.35)	-1.3 (13.26)
Week 21, n=127, 125	0.4 (13.97)	-0.2 (14.38)
Week 33, n=71, 65	1.1 (14.80)	-1.7 (10.81)
Week 45, n=34, 39	0.9 (17.68)	-1.6 (10.41)
Withdrawal, n=193, 214	-4.4 (16.11)	-7.5 (15.02)

13. Secondary Outcome

Title	Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores
Description	The TOI questionnaire was designed to measure multidimensional QOL in participants with cancer and includes subscales for physical, functional well-being, and additional cancer concerns. The physical and functional well-being subscale scores range from 0 to 28, based on 7 questions (each question scored from 0 [not at all] to 4 [very much]); the breast cancer unweighted subscale scores range from 0 to 36, based on 9 questions. The total TOI score (ranging from 0 [better QOL] to 92 [worse QOL]) is the sum of the TOI subscale scores.
Time Frame	Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants contributing data at the indicated time points were analyzed. Only observed data were collected, and score analyses were conducted using the LOCF method.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	208	232
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Week 9, n=208, 232	-2.3 (12.32)	-2.6 (11.88)
Week 21, n=126, 125	-0.5 (11.99)	-2.7 (12.42)
Week 33, n=72, 65	-0.1 (12.83)	-2.9 (9.05)
Week 45, n=36, 38	1.5 (15.91)	-2.8 (8.98)
Withdrawal, n=190, 212	-4.4 (14.30)	-6.1 (12.84)

14. Secondary Outcome

Title	Number of Participants With the Indicated ErbB2 Status at Baseline
Description	The Press Laboratory collected tumor tissues of participants for ErbB2 testing. ErbB2 testing is done to detect breast cancer and predict its likely outcome. All samples were analyzed by the Press Laboratory. Participants were categorized as ErbB2 positive (overexpression of the ErbB2 gene), ErbB2 negative, and assay not done (which included participants with no available samples and those with inconclusive results). ErbB2 status is determined by immunohistochemistry (ICH) assay and fluorescence in situ hybridization (FISH) testing. Negative ErbB2 status is defined as 0 or 1+ by IHC, or as 2+ by IHC and FISH.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: participants
Positive	52	39
Negative	199	202
Assay not done	40	47

15. Secondary Outcome

Title	ErbB2 Ratio
Description	The Press Laboratory collected tumor tissues of participants for biomarker testing. All samples were analyzed by the Press Laboratory. The ratio of ErbB2 gene signals to chromosome 17 signals, which indicates the progression of breast cancer, was calculated. Low levels of amplification (few copies) may have a ratio of 2-5, whereas high levels of amplification may have a ratio >10.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants contributing data at the indicated time points were analyzed. Only observed data were collected, and score analyses were conducted using the LOCF method.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	220	200
Mean (Standard Deviation); Unit of Measure: ratio of signals
	2.23 (2.301)	2.14 (2.214)

16. Secondary Outcome

Title	Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening
Description	The Press Laboratory tested tumor tissue samples (taken at Screening, prior to randomization to study treatment) to determine intra-tumoral expression levels of ErbB1, ErbB2, and other analytes associated with these pathways by IHC, the process of detecting antigens (e.g., proteins) in cells of a tissue section. The IHC assessment is expressed as: 0, no staining (no cancer cells); 1+, faint staining; 2+, weak to moderate complete staining; 3+, strong complete staining (many cancer cells). A status of "Assay not done" was assigned to participants with no available samples and to those with inconclusive results. If strong staining is observed, breast cancer that has high levels of HER2 expression (overexpression) is indicated. If moderate/weak staining is observed (IHC=2+), breast cancer that has low/moderate expression levels is indicated. When no staining is observed (IHC=0), breast cancer HER2 expression may be below the level of detection of the assay.
Time Frame	Screening (Day -1)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: participants
0	139	139
1+	50	51
2+	15	22
3+	40	28
Assay not done	47	48

17. Secondary Outcome

Title	Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results
Description	The Press Laboratory tested participants who were 2+ (weak to moderate complete staining) or 3+ (strong complete staining) for ErbB2 overexpression by IHC for ErbB2 gene amplification using the FISH assay. The results of the FISH assay can be ErbB2 gene "amplification" (increased number of copies of the ErbB2 gene) or "non-amplification" (not many copies of the ErbB2 gene). A status of "Assay not done" was assigned to those participants with no available samples and to those with inconclusive results (e.g., due to hybridization or staining problems).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	291	288
Measure Type: Number; Unit of Measure: participants
Amplified	45	35
Non-amplified	175	165
Assay not done	71	88

18. Secondary Outcome

Title	Serum ErbB1 Concentration
Description	The Quest Laboratory collected blood samples for quantitative determination of serum ErbB1. The results of serum monitoring were used to compare tumor response rates following randomized therapy.
Time Frame	Screening (Day-1) and Withdrawal (up to Study Week 129)

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants contributing data at the indicated time points were analyzed. Only observed data were collected, and score analyses were conducted using the LOCF method.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	269	265
Mean (Standard Deviation); Unit of Measure: Nanograms per milliliter (ng/mL)
Screening, n=269, 265	58.6 (20.30)	59.5 (44.20)
Withdrawal, n=145, 157	59.0 (30.22)	61.5 (16.74)

19. Secondary Outcome

Title	Serum ErbB2 Concentration
Description	The Quest Laboratory collected blood samples for quantitative determination of serum ErbB2. The results of serum monitoring were used to compare tumor response rates following randomized therapy.
Time Frame	Screening (Day-1) and Withdrawal (up to Study Week 129)

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants contributing data at the indicated time points were analyzed. Only observed data were collected, and score analyses were conducted using the LOCF method.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	270	265
Mean (Standard Deviation); Unit of Measure: ng/mL
Screening, n=270, 265	37.67 (95.883)	36.19 (87.629)
Withdrawal, n=145, 158	37.31 (98.257)	39.95 (96.327)

20. Secondary Outcome

Title	Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4
Description	The severity of adverse events was graded per the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3. Grades 1 through 5 have unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1, Mild AE; Grade 2, Moderate AE; Grade 3, Severe AE; Grade 4, Life-threatening or disabling AE; Grade 5, death related to AE.
Time Frame	Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population: all randomized participants 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). Two participants randomized to the placebo group actually received lapatinib.

Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description:	Participants received lapatinib 1500 mg orally OD with paclitaxel 175 m^2 IV over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed	293	286
Measure Type: Number; Unit of Measure: participants
Diarrhea; Grade 3	43	4
Diarrhea; Grade 4	1	0
Alopecia; Grade 3	10	15
Alopecia; Grade 4	0	0
Rash; Grade 3	15	1
Rash; Grade 4	0	0
Nausea; Grade 3	7	2
Nausea; Grade 4	0	0
Myalgia; Grade 3	6	2
Myalgia; Grade 4	0	0
Neutropenia; Grade 3	30	20
Neutropenia; Grade 4	23	14
Vomiting; Grade 3	5	4
Vomiting; Grade 4	0	0
Arthralgia; Grade 3	7	4
Arthralgia; Grade 4	0	0
Fatigue; Grade 3	5	5
Fatigue; Grade 4	0	0
Asthenia; Grade 3	1	4
Asthenia; Grade 4	1	0
Neuropathy; Grade 3	7	3
Neuropathy; Grade 4	0	0
Decreased appetite; Grade 3	1	0
Decreased appetite; Grade 4	0	0
Pain in extremity; Grade 3	2	3
Pain in extremity; Grade 4	2	0
Peripheral sensory neuropathy; Grade 3	6	4
Peripheral sensory neuropathy; Grade 4	0	0
Pruritis; Grade 3	2	0
Pruritis; Grade 4	0	0
Paraesthesia; Grade 3	2	1
Paraesthesia; Grade 4	0	0
Constipation; Grade 3	0	0
Constipation; Grade 4	0	0
Cough; Grade 3	1	1
Cough; Grade 4	0	0

Adverse Events

Time Frame	Serious adverse events (SAEs) and adverse events were collected from the first dose of randomized therapy until 30 days after the last dose of randomized therapy (average of 26 weeks).
Adverse Event Reporting Description	SAEs and AEs were collected in the Safety Population, comprised of all randomized participants 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). Two participants randomized to the placebo group actually received lapatinib.
Arm/Group Title	Lapatinib With Paclitaxel	Placebo With Paclitaxel
Arm/Group Description	Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.	Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
All-Cause Mortality
	Lapatinib With Paclitaxel	Placebo With Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Lapatinib With Paclitaxel	Placebo With Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	103/293 (35.15%)	63/286 (22.03%)
Blood and lymphatic system disorders
Neutropenia † 1	22/293 (7.51%)	14/286 (4.90%)
Febrile neutropenia † 1	10/293 (3.41%)	3/286 (1.05%)
Disseminated intravascular coagulation † 1	0/293 (0.00%)	1/286 (0.35%)
Leukopenia † 1	0/293 (0.00%)	1/286 (0.35%)
Thrombocythemia † 1	1/293 (0.34%)	0/286 (0.00%)
Cardiac disorders
Left ventricular dysfunction † 1	2/293 (0.68%)	1/286 (0.35%)
Atrial fibrillation † 1	1/293 (0.34%)	0/286 (0.00%)
Cardiac arrest † 1	1/293 (0.34%)	0/286 (0.00%)
Cardiac failure † 1	1/293 (0.34%)	0/286 (0.00%)
Myocardial infarction † 1	0/293 (0.00%)	1/286 (0.35%)
Ventricular arrhythmia † 1	1/293 (0.34%)	0/286 (0.00%)
Eye disorders
Retinal detachment † 1	1/293 (0.34%)	1/286 (0.35%)
Ulcerative keratitis † 1	1/293 (0.34%)	0/286 (0.00%)
Pterygium † 1	1/293 (0.34%)	0/286 (0.00%)
Gastrointestinal disorders
Diarrhea † 1	24/293 (8.19%)	2/286 (0.70%)
Vomiting † 1	4/293 (1.37%)	4/286 (1.40%)
Abdominal pain † 1	2/293 (0.68%)	0/286 (0.00%)
Nausea † 1	1/293 (0.34%)	1/286 (0.35%)
Ascites † 1	1/293 (0.34%)	0/286 (0.00%)
Constipation † 1	0/293 (0.00%)	1/286 (0.35%)
Gastrointestinal toxicity † 1	1/293 (0.34%)	0/286 (0.00%)
Ileus † 1	1/293 (0.34%)	0/286 (0.00%)
Intestinal ischemia † 1	1/293 (0.34%)	0/286 (0.00%)
Esophagitis † 1	1/293 (0.34%)	0/286 (0.00%)
Rectal hemorrhage † 1	0/293 (0.00%)	1/286 (0.35%)
Stomatitis † 1	1/293 (0.34%)	0/286 (0.00%)
General disorders
Pyrexia † 1	7/293 (2.39%)	2/286 (0.70%)
Mucosal inflammation † 1	6/293 (2.05%)	1/286 (0.35%)
Chest pain † 1	2/293 (0.68%)	2/286 (0.70%)
Asthenia † 1	1/293 (0.34%)	0/286 (0.00%)
Death † 1	0/293 (0.00%)	1/286 (0.35%)
Edema peripheral † 1	1/293 (0.34%)	0/286 (0.00%)
Performance status decreased † 1	1/293 (0.34%)	0/286 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	1/293 (0.34%)	0/286 (0.00%)
Cholecystitis chronic † 1	0/293 (0.00%)	1/286 (0.35%)
Cholelithiasis † 1	1/293 (0.34%)	0/286 (0.00%)
Hepatotoxicity † 1	1/293 (0.34%)	0/286 (0.00%)
Jaundice cholestatic † 1	0/293 (0.00%)	1/286 (0.35%)
Immune system disorders
Hypersensitivity † 1	2/293 (0.68%)	1/286 (0.35%)
Anaphylactic reaction † 1	1/293 (0.34%)	0/286 (0.00%)
Infections and infestations
Pneumonia † 1	3/293 (1.02%)	2/286 (0.70%)
Device related infection † 1	2/293 (0.68%)	1/286 (0.35%)
Sepsis † 1	2/293 (0.68%)	1/286 (0.35%)
Septic shock † 1	2/293 (0.68%)	0/286 (0.00%)
Staphylococcal infection † 1	1/293 (0.34%)	1/286 (0.35%)
Urinary tract infection † 1	2/293 (0.68%)	0/286 (0.00%)
Acarodermatitis † 1	1/293 (0.34%)	0/286 (0.00%)
Breast abscess † 1	0/293 (0.00%)	1/286 (0.35%)
Bronchopneumonia † 1	0/293 (0.00%)	1/286 (0.35%)
Catheter site infection † 1	1/293 (0.34%)	0/286 (0.00%)
Cellulitis † 1	0/293 (0.00%)	1/286 (0.35%)
Enterocolitis infectious † 1	1/293 (0.34%)	0/286 (0.00%)
Gallbladder abscess † 1	1/293 (0.34%)	0/286 (0.00%)
Lower respiratory tract infection † 1	1/293 (0.34%)	0/286 (0.00%)
Lung infection † 1	0/293 (0.00%)	1/286 (0.35%)
Lymphangitis † 1	1/293 (0.34%)	0/286 (0.00%)
Oral candidiasis † 1	1/293 (0.34%)	0/286 (0.00%)
Pneumonia primary atypical † 1	1/293 (0.34%)	0/286 (0.00%)
Pyelonephritis † 1	0/293 (0.00%)	1/286 (0.35%)
Skin infection † 1	0/293 (0.00%)	1/286 (0.35%)
Urosepsis † 1	0/293 (0.00%)	1/286 (0.35%)
Injury, poisoning and procedural complications
Ankle fracture † 1	0/293 (0.00%)	1/286 (0.35%)
Femur fracture † 1	1/293 (0.34%)	0/286 (0.00%)
Foot fracture † 1	1/293 (0.34%)	0/286 (0.00%)
Poisoning † 1	1/293 (0.34%)	0/286 (0.00%)
Investigations
Ejection fraction decreased † 1	5/293 (1.71%)	5/286 (1.75%)
Hemoglobin decreased † 1	1/293 (0.34%)	1/286 (0.35%)
Alanine aminotransferase increased † 1	1/293 (0.34%)	0/286 (0.00%)
Blood creatinine increased † 1	0/293 (0.00%)	1/286 (0.35%)
Blood uric acid increased † 1	0/293 (0.00%)	1/286 (0.35%)
Body temperature increased † 1	1/293 (0.34%)	0/286 (0.00%)
Neutrophil count decreased † 1	1/293 (0.34%)	0/286 (0.00%)
Metabolism and nutrition disorders
Hypercalcemia † 1	4/293 (1.37%)	3/286 (1.05%)
Dehydration † 1	4/293 (1.37%)	0/286 (0.00%)
Hypokalemia † 1	2/293 (0.68%)	0/286 (0.00%)
Fluid overload † 1	0/293 (0.00%)	1/286 (0.35%)
Hyperglycemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hyperkalemia † 1	0/293 (0.00%)	1/286 (0.35%)
Hypernatremia † 1	0/293 (0.00%)	1/286 (0.35%)
Hyperuricemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hypocalcemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hypoglycemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hypomagnesemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hyponatremia † 1	1/293 (0.34%)	0/286 (0.00%)
Hypovolemia † 1	1/293 (0.34%)	0/286 (0.00%)
Tetany † 1	1/293 (0.34%)	0/286 (0.00%)
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	3/293 (1.02%)	0/286 (0.00%)
Arthralgia † 1	2/293 (0.68%)	0/286 (0.00%)
Pathological fracture † 1	1/293 (0.34%)	1/286 (0.35%)
Back pain † 1	1/293 (0.34%)	0/286 (0.00%)
Intervertebral disc disorder † 1	0/293 (0.00%)	1/286 (0.35%)
Joint effusion † 1	1/293 (0.34%)	0/286 (0.00%)
Muscular weakness † 1	1/293 (0.34%)	0/286 (0.00%)
Myalgia † 1	0/293 (0.00%)	1/286 (0.35%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer † 1	0/293 (0.00%)	1/286 (0.35%)
Metastases to central nervous system † 1	1/293 (0.34%)	0/286 (0.00%)
Tumor hemorrhage † 1	1/293 (0.34%)	0/286 (0.00%)
Nervous system disorders
Convulsion † 1	1/293 (0.34%)	1/286 (0.35%)
Cerebral infarction † 1	0/293 (0.00%)	1/286 (0.35%)
Cerebrovascular disorder † 1	1/293 (0.34%)	0/286 (0.00%)
Headache † 1	1/293 (0.34%)	0/286 (0.00%)
Hemiplegia † 1	0/293 (0.00%)	1/286 (0.35%)
Lumber radiculopathy † 1	0/293 (0.00%)	1/286 (0.35%)
Mental impairment † 1	1/293 (0.34%)	0/286 (0.00%)
Neuralgia † 1	1/293 (0.34%)	0/286 (0.00%)
Peripheral motor neuropathy † 1	0/293 (0.00%)	1/286 (0.35%)
Peripheral sensory neuropathy † 1	0/293 (0.00%)	1/286 (0.35%)
Somnolence † 1	1/293 (0.34%)	0/286 (0.00%)
Syncope † 1	1/293 (0.34%)	0/286 (0.00%)
Psychiatric disorders
Anxiety † 1	0/293 (0.00%)	1/286 (0.35%)
Confusional state † 1	0/293 (0.00%)	1/286 (0.35%)
Mental status changes † 1	0/293 (0.00%)	1/286 (0.35%)
Renal and urinary disorders
Renal colic † 1	1/293 (0.34%)	0/286 (0.00%)
Renal failure acute † 1	1/293 (0.34%)	0/286 (0.00%)
Urinary retention † 1	0/293 (0.00%)	1/286 (0.35%)
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	3/293 (1.02%)	3/286 (1.05%)
Pulmonary embolism † 1	2/293 (0.68%)	0/286 (0.00%)
Cough † 1	1/293 (0.34%)	0/286 (0.00%)
Epistaxis † 1	1/293 (0.34%)	0/286 (0.00%)
Hemothorax † 1	0/293 (0.00%)	1/286 (0.35%)
Hypoxia † 1	0/293 (0.00%)	1/286 (0.35%)
Pleural effusion † 1	0/293 (0.00%)	1/286 (0.35%)
Pneumonitis † 1	0/293 (0.00%)	1/286 (0.35%)
Pulmonary hemorrhage † 1	1/293 (0.34%)	0/286 (0.00%)
Pulmonary edema † 1	1/293 (0.34%)	0/286 (0.00%)
Wheezing † 1	1/293 (0.34%)	0/286 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	4/293 (1.37%)	0/286 (0.00%)
Erythema multiforme † 1	1/293 (0.34%)	0/286 (0.00%)
Intertrigo † 1	0/293 (0.00%)	1/286 (0.35%)
Rash erythematous † 1	1/293 (0.34%)	0/286 (0.00%)
Rash generalized † 1	0/293 (0.00%)	1/286 (0.35%)
Vascular disorders
Hypotension † 1	3/293 (1.02%)	0/286 (0.00%)
Thrombosis † 1	1/293 (0.34%)	2/286 (0.70%)
Deep vein thrombosis † 1	2/293 (0.68%)	0/286 (0.00%)
Hypertension † 1	0/293 (0.00%)	2/286 (0.70%)
Embolism † 1	1/293 (0.34%)	0/286 (0.00%)
Hemorrhage † 1	1/293 (0.34%)	0/286 (0.00%)
Hypertensive crisis † 1	1/293 (0.34%)	0/286 (0.00%)
Phlebitis † 1	0/293 (0.00%)	1/286 (0.35%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Lapatinib With Paclitaxel	Placebo With Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	287/293 (97.95%)	278/286 (97.20%)
Blood and lymphatic system disorders
Neutropenia † 1	76/293 (25.94%)	58/286 (20.28%)
Anemia † 1	32/293 (10.92%)	35/286 (12.24%)
Leukopenia † 1	26/293 (8.87%)	25/286 (8.74%)
Febrile neutropenia † 1	12/293 (4.10%)	4/286 (1.40%)
Leukocytosis † 1	2/293 (0.68%)	5/286 (1.75%)
Thrombocytopenia † 1	2/293 (0.68%)	4/286 (1.40%)
Lymphopenia † 1	2/293 (0.68%)	1/286 (0.35%)
Lymph node pain † 1	1/293 (0.34%)	1/286 (0.35%)
Thrombocytosis † 1	1/293 (0.34%)	1/286 (0.35%)
Disseminated intravascular coagulation † 1	0/293 (0.00%)	1/286 (0.35%)
Eosinophilia † 1	1/293 (0.34%)	0/286 (0.00%)
Hyperchromasia † 1	1/293 (0.34%)	0/286 (0.00%)
Monocytosis † 1	1/293 (0.34%)	0/286 (0.00%)
Pancytopenia † 1	1/293 (0.34%)	0/286 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	4/293 (1.37%)	7/286 (2.45%)
Tinnitus † 1	2/293 (0.68%)	1/286 (0.35%)
Deafness † 1	1/293 (0.34%)	0/286 (0.00%)
Ear pain † 1	1/293 (0.34%)	0/286 (0.00%)
Hypoacusis † 1	0/293 (0.00%)	1/286 (0.35%)
Endocrine disorders
Cushingoid † 1	1/293 (0.34%)	0/286 (0.00%)
Hypothyroidism † 1	0/293 (0.00%)	1/286 (0.35%)
Gastrointestinal disorders
Diarrhea † 1	171/293 (58.36%)	73/286 (25.52%)
Nausea † 1	100/293 (34.13%)	85/286 (29.72%)
Vomiting † 1	74/293 (25.26%)	48/286 (16.78%)
Constipation † 1	35/293 (11.95%)	48/286 (16.78%)
Dyspepsia † 1	38/293 (12.97%)	13/286 (4.55%)
Abdominal pain † 1	33/293 (11.26%)	17/286 (5.94%)
Stomatitis † 1	21/293 (7.17%)	13/286 (4.55%)
Abdominal pain upper † 1	12/293 (4.10%)	16/286 (5.59%)
Abdominal distension † 1	14/293 (4.78%)	9/286 (3.15%)
Dry mouth † 1	9/293 (3.07%)	5/286 (1.75%)
Hemorrhoids † 1	6/293 (2.05%)	4/286 (1.40%)
Flatulence † 1	5/293 (1.71%)	3/286 (1.05%)
Gastroesophageal reflux disease † 1	4/293 (1.37%)	4/286 (1.40%)
Dysphagia † 1	5/293 (1.71%)	2/286 (0.70%)
Cheilitis † 1	3/293 (1.02%)	3/286 (1.05%)
Epigastric discomfort † 1	2/293 (0.68%)	4/286 (1.40%)
Mouth ulceration † 1	2/293 (0.68%)	0/286 (0.00%)
Esophagitis † 1	4/293 (1.37%)	1/286 (0.35%)
Abdominal discomfort † 1	2/293 (0.68%)	3/286 (1.05%)
Colitis † 1	3/293 (1.02%)	1/286 (0.35%)
Gastritis † 1	2/293 (0.68%)	2/286 (0.70%)
Retching † 1	1/293 (0.34%)	3/286 (1.05%)
Toothache † 1	3/293 (1.02%)	1/286 (0.35%)
Abdominal pain lower † 1	2/293 (0.68%)	1/286 (0.35%)
Anal hemorrhage † 1	3/293 (1.02%)	0/286 (0.00%)
Rectal hemorrhage † 1	1/293 (0.34%)	2/286 (0.70%)
Abdominal tenderness † 1	2/293 (0.68%)	0/286 (0.00%)
Apthous stomatitis † 1	2/293 (0.68%)	0/286 (0.00%)
Ascites † 1	1/293 (0.34%)	1/286 (0.35%)
Gingival pain † 1	0/293 (0.00%)	1/286 (0.35%)
Gingivitis † 1	1/293 (0.34%)	1/286 (0.35%)
Hematochezia † 1	1/293 (0.34%)	1/286 (0.35%)
Oral discomfort † 1	0/293 (0.00%)	2/286 (0.70%)
Oral pain † 1	2/293 (0.68%)	0/286 (0.00%)
Proctalgia † 1	2/293 (0.68%)	0/286 (0.00%)
Abdominal rigidity † 1	1/293 (0.34%)	0/286 (0.00%)
Anorectal discomfort † 1	1/293 (0.34%)	0/286 (0.00%)
Anal fissure † 1	1/293 (0.34%)	0/286 (0.00%)
Anal ulcer † 1	0/293 (0.00%)	1/286 (0.35%)
Diabetic gastropathy † 1	1/293 (0.34%)	0/286 (0.00%)
Fecaloma † 1	1/293 (0.34%)	0/286 (0.00%)
Gastric disorder † 1	0/293 (0.00%)	1/286 (0.35%)
Gastrointestinal pain † 1	0/293 (0.00%)	1/286 (0.35%)
Gastrointestinal toxicity † 1	1/293 (0.34%)	0/286 (0.00%)
Gingival bleeding † 1	0/293 (0.00%)	1/286 (0.35%)
Glossodynia † 1	1/293 (0.34%)	0/286 (0.00%)
Hemorrhoidal hemorrhage † 1	1/293 (0.34%)	0/286 (0.00%)
Hiatus hernia † 1	0/293 (0.00%)	1/286 (0.35%)
Hyperchlorhydria † 1	1/293 (0.34%)	0/286 (0.00%)
Hypoaesthesia oral † 1	1/293 (0.34%)	0/286 (0.00%)
Ileus † 1	1/293 (0.34%)	0/286 (0.00%)
Impaired gastric emptying † 1	1/293 (0.34%)	0/286 (0.00%)
Intestinal ischemia † 1	1/293 (0.34%)	0/286 (0.00%)
Lip dry † 1	0/293 (0.00%)	1/286 (0.35%)
Lip edema † 1	1/293 (0.34%)	0/286 (0.00%)
Loose tooth † 1	0/293 (0.00%)	1/286 (0.35%)
Melena † 1	1/293 (0.34%)	0/286 (0.00%)
Odynophagia † 1	1/293 (0.34%)	0/286 (0.00%)
Esophageal discomfort † 1	1/293 (0.34%)	0/286 (0.00%)
Pancreatitis † 1	0/293 (0.00%)	1/286 (0.35%)
Parasthesia oral † 1	1/293 (0.34%)	0/286 (0.00%)
Reflux gastritis † 1	0/293 (0.00%)	1/286 (0.35%)
Subileus † 1	1/293 (0.34%)	0/286 (0.00%)
Tongue pigmentation † 1	1/293 (0.34%)	0/286 (0.00%)
Tongue ulceration † 1	1/293 (0.34%)	0/286 (0.00%)
General disorders
Fatigue † 1	65/293 (22.18%)	61/286 (21.33%)
Asthenia † 1	62/293 (21.16%)	36/286 (12.59%)
Pyrexia † 1	32/293 (10.92%)	33/286 (11.54%)
Mucosal inflammation † 1	38/293 (12.97%)	9/286 (3.15%)
Edema perpheral † 1	18/293 (6.14%)	19/286 (6.64%)
Pain † 1	19/293 (6.48%)	16/286 (5.59%)
Chest pain † 1	19/293 (6.48%)	14/286 (4.90%)
Chills † 1	6/293 (2.05%)	8/286 (2.80%)
Malaise † 1	6/293 (2.05%)	7/286 (2.45%)
Chest discomfort † 1	6/293 (2.05%)	4/286 (1.40%)
Axillary pain † 1	4/293 (1.37%)	4/286 (1.40%)
Influenza like illness † 1	4/293 (1.37%)	5/286 (1.75%)
Face edema † 1	4/293 (1.37%)	2/286 (0.70%)
Edema † 1	3/293 (1.02%)	3/286 (1.05%)
Catheter site pain † 1	1/293 (0.34%)	2/286 (0.70%)
Inflammation † 1	3/293 (1.02%)	0/286 (0.00%)
Adverse drug reaction † 1	0/293 (0.00%)	2/286 (0.70%)
Discomfort † 1	0/293 (0.00%)	2/286 (0.70%)
Injection site reaction † 1	1/293 (0.34%)	1/286 (0.35%)
Irritability † 1	0/293 (0.00%)	2/286 (0.70%)
Breakthrough pain † 1	1/293 (0.34%)	0/286 (0.00%)
Catheter site inflammation † 1	1/293 (0.34%)	0/286 (0.00%)
Catheter site related reaction † 1	1/293 (0.34%)	0/286 (0.00%)
Death † 1	0/293 (0.00%)	1/286 (0.35%)
Early satiety † 1	0/293 (0.00%)	1/286 (0.35%)
Extravasation † 1	1/293 (0.34%)	0/286 (0.00%)
Facial pain † 1	1/293 (0.34%)	0/286 (0.00%)
Granuloma † 1	0/293 (0.00%)	1/286 (0.35%)
Implant site scar † 1	1/293 (0.34%)	0/286 (0.00%)
Infusion site extravasation † 1	0/293 (0.00%)	1/286 (0.35%)
Infusion site edema † 1	0/293 (0.00%)	1/286 (0.35%)
Infusion site pain † 1	0/293 (0.00%)	1/286 (0.35%)
Local swelling † 1	0/293 (0.00%)	1/286 (0.35%)
Localized edema † 1	1/293 (0.34%)	0/286 (0.00%)
Non-cardiac chest pain † 1	0/293 (0.00%)	1/286 (0.35%)
Performance status decreased † 1	1/293 (0.34%)	0/286 (0.00%)
Vessel puncture site pain † 1	1/293 (0.34%)	0/286 (0.00%)
Thirst † 1	1/293 (0.34%)	0/286 (0.00%)
Vessel puncture site reaction † 1	1/293 (0.34%)	0/286 (0.00%)
Generalized edema † 1	0/293 (0.00%)	1/286 (0.35%)
Injection site pain † 1	1/293 (0.34%)	0/286 (0.00%)
Hepatobiliary disorders
Hyperbilirubinemia † 1	6/293 (2.05%)	4/286 (1.40%)
Jaundice † 1	2/293 (0.68%)	1/286 (0.35%)
Cholecystitis † 1	2/293 (0.68%)	0/286 (0.00%)
Hepatotoxicity † 1	1/293 (0.34%)	1/286 (0.35%)
Cholecystitis chronic † 1	0/293 (0.00%)	1/286 (0.35%)
Cholelithiasis † 1	1/293 (0.34%)	0/286 (0.00%)
Jaundice cholestatic † 1	0/293 (0.00%)	1/286 (0.35%)
Immune system disorders
Hypersensitivity † 1	11/293 (3.75%)	3/286 (1.05%)
Drug hypersensitivity † 1	3/293 (1.02%)	1/286 (0.35%)
Anaphylactic reaction † 1	1/293 (0.34%)	1/286 (0.35%)
Anaphylactic shock † 1	1/293 (0.34%)	0/286 (0.00%)
Multiple allergies † 1	0/293 (0.00%)	1/286 (0.35%)
Contrast media allergy † 1	1/293 (0.34%)	0/286 (0.00%)
Infections and infestations
Nasopharyngitis † 1	17/293 (5.80%)	7/286 (2.45%)
Upper respiratory tract infection † 1	8/293 (2.73%)	15/286 (5.24%)
Urinary tract infection † 1	15/293 (5.12%)	8/286 (2.80%)
Influenza † 1	5/293 (1.71%)	9/286 (3.15%)
Pharyngitis † 1	9/293 (3.07%)	3/286 (1.05%)
Cellulitis † 1	4/293 (1.37%)	5/286 (1.75%)
Rhinitis † 1	7/293 (2.39%)	2/286 (0.70%)
Pneumonia † 1	4/293 (1.37%)	4/286 (1.40%)
Bronchitis † 1	5/293 (1.71%)	4/286 (1.40%)
Infection † 1	6/293 (2.05%)	1/286 (0.35%)
Respiratory tract infection † 1	5/293 (1.71%)	2/286 (0.70%)
Cystitis † 1	2/293 (0.68%)	4/286 (1.40%)
Herpes simplex † 1	1/293 (0.34%)	1/286 (0.35%)
Herpes zoster † 1	3/293 (1.02%)	3/286 (1.05%)
Oral candidiasis † 1	4/293 (1.37%)	2/286 (0.70%)
Device related infection † 1	2/293 (0.68%)	3/286 (1.05%)
Folliculitis † 1	3/293 (1.02%)	2/286 (0.70%)
Oral herpes † 1	5/293 (1.71%)	0/286 (0.00%)
Acarodermatitis † 1	4/293 (1.37%)	0/286 (0.00%)
Fungal infection † 1	2/293 (0.68%)	1/286 (0.35%)
Laryngitis † 1	1/293 (0.34%)	3/286 (1.05%)
Lung infection † 1	1/293 (0.34%)	3/286 (1.05%)
Paronychia † 1	5/293 (1.71%)	0/286 (0.00%)
Breast infection † 1	0/293 (0.00%)	3/286 (1.05%)
Lower respiratory tract infection † 1	2/293 (0.68%)	1/286 (0.35%)
Nail infection † 1	3/293 (1.02%)	0/286 (0.00%)
Sepsis † 1	2/293 (0.68%)	1/286 (0.35%)
Sinusitis † 1	1/293 (0.34%)	2/286 (0.70%)
Tonsillitis † 1	3/293 (1.02%)	0/286 (0.00%)
Candidiasis † 1	2/293 (0.68%)	0/286 (0.00%)
Catheter site infection † 1	1/293 (0.34%)	1/286 (0.35%)
Gastroenteritis † 1	2/293 (0.68%)	0/286 (0.00%)
Kidney infection † 1	2/293 (0.68%)	0/286 (0.00%)
Lymphangitis † 1	2/293 (0.68%)	0/286 (0.00%)
Otiits externa † 1	2/293 (0.68%)	0/286 (0.00%)
Otitis media chronic † 1	2/293 (0.68%)	0/286 (0.00%)
Respiratory tract infection viral † 1	0/293 (0.00%)	2/286 (0.70%)
Septic shock † 1	2/293 (0.68%)	0/286 (0.00%)
Skin infection † 1	0/293 (0.00%)	2/286 (0.70%)
Staphylococcal infection † 1	1/293 (0.34%)	1/286 (0.35%)
Viral infection † 1	2/293 (0.68%)	0/286 (0.00%)
Vulvovaginal mycotic infection † 1	2/293 (0.68%)	0/286 (0.00%)
Breast abscess † 1	0/293 (0.00%)	1/286 (0.35%)
Bronchopneumonia † 1	0/293 (0.00%)	1/286 (0.35%)
Catheter site cellulitis † 1	1/293 (0.34%)	0/286 (0.00%)
Clostridial infection † 1	0/293 (0.00%)	1/286 (0.35%)
Clostridium difficile colitis † 1	1/293 (0.34%)	0/286 (0.00%)
Enterocolitis infection † 1	1/293 (0.34%)	0/286 (0.00%)
Epstein-Barr virus infection † 1	1/293 (0.34%)	0/286 (0.00%)
Erysipelas † 1	1/293 (0.34%)	0/286 (0.00%)
Furuncle † 1	1/293 (0.34%)	0/286 (0.00%)
Gallbladder abscess † 1	1/293 (0.34%)	0/286 (0.00%)
Gastrointestinal fungal infection † 1	1/293 (0.34%)	0/286 (0.00%)
Fungal skin infection † 1	0/293 (0.00%)	3/286 (1.05%)
Genital candidiasis † 1	1/293 (0.34%)	0/286 (0.00%)
Klebsiella infection † 1	1/293 (0.34%)	0/286 (0.00%)
Localized infection † 1	1/293 (0.34%)	0/286 (0.00%)
Omphalitis † 1	1/293 (0.34%)	0/286 (0.00%)
Oral fungal infection † 1	1/293 (0.34%)	0/286 (0.00%)
Pneumonia primary atypical † 1	1/293 (0.34%)	0/286 (0.00%)
Postoperative wound infection † 1	1/293 (0.34%)	0/286 (0.00%)
Pyelonephritis † 1	0/293 (0.00%)	1/286 (0.35%)
Subcutaneous abscess † 1	1/293 (0.34%)	0/286 (0.00%)
Tooth abscess † 1	1/293 (0.34%)	0/286 (0.00%)
Tuberculosis † 1	0/293 (0.00%)	1/286 (0.35%)
Urosepsis † 1	0/293 (0.00%)	1/286 (0.35%)
Vaginal infection † 1	1/293 (0.34%)	0/286 (0.00%)
Viral rash † 1	1/293 (0.34%)	0/286 (0.00%)
Viral upper respiratory tract infection † 1	1/293 (0.34%)	0/286 (0.00%)
Injury, poisoning and procedural complications
Upper limb fracture † 1	0/293 (0.00%)	1/286 (0.35%)
Wound secretion † 1	1/293 (0.34%)	0/286 (0.00%)
Investigations
Alanine aminotransferase increased † 1	27/293 (9.22%)	23/286 (8.04%)
Aspartete aminotransferase increased † 1	22/293 (7.51%)	20/286 (6.99%)
Blood alkaline phosphatase increased † 1	19/293 (6.48%)	19/286 (6.64%)
Weight decreased † 1	17/293 (5.80%)	14/286 (4.90%)
Ejection fraction decreased † 1	6/293 (2.05%)	6/286 (2.10%)
Hemoglobin decreased † 1	8/293 (2.73%)	4/286 (1.40%)
Blood urea increased † 1	2/293 (0.68%)	3/286 (1.05%)
Weight increased † 1	1/293 (0.34%)	9/286 (3.15%)
Neutrophil count decreased † 1	5/293 (1.71%)	3/286 (1.05%)
White blood cell count decreased † 1	5/293 (1.71%)	1/286 (0.35%)
Body temperature increased † 1	2/293 (0.68%)	3/286 (1.05%)
Gamma-glutamyltransferase increased † 1	3/293 (1.02%)	2/286 (0.70%)
Blood albumin decreased † 1	3/293 (1.02%)	1/286 (0.35%)
Blood creatinine increased † 1	2/293 (0.68%)	2/286 (0.70%)
Blood lactate dehydogenase increased † 1	2/293 (0.68%)	2/286 (0.70%)
Blood bilirubin increased † 1	2/293 (0.68%)	1/286 (0.35%)
Blood potassium decreased † 1	2/293 (0.68%)	1/286 (0.35%)
Blood glucose increased † 1	1/293 (0.34%)	1/286 (0.35%)
Blood uric acid increased † 1	0/293 (0.00%)	2/286 (0.70%)
International normalized ratio increased † 1	2/293 (0.68%)	0/286 (0.00%)
Activated partial thromboplastin time prolonged † 1	1/293 (0.34%)	0/286 (0.00%)
Blood bilirubin decreased † 1	1/293 (0.34%)	0/286 (0.00%)
Blood calcium decreased † 1	1/293 (0.34%)	0/286 (0.00%)
Blood homocysteine increased † 1	1/293 (0.34%)	0/286 (0.00%)
Blood pressure increased † 1	1/293 (0.34%)	0/286 (0.00%)
Blood sodium increased † 1	1/293 (0.34%)	0/286 (0.00%)
Blood urine present † 1	1/293 (0.34%)	0/286 (0.00%)
Hemoglobin † 1	1/293 (0.34%)	0/286 (0.00%)
Heart rate irregular † 1	1/293 (0.34%)	0/286 (0.00%)
Platelet count decreased † 1	0/293 (0.00%)	1/286 (0.35%)
Prothrombin level decreased † 1	1/293 (0.34%)	0/286 (0.00%)
Prothrombin time prolonged † 1	1/293 (0.34%)	0/286 (0.00%)
White blood cell count increased † 1	1/293 (0.34%)	0/286 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	50/293 (17.06%)	32/286 (11.19%)
Hypercalcemia † 1	7/293 (2.39%)	8/286 (2.80%)
Hyperglycemia † 1	7/293 (2.39%)	8/286 (2.80%)
Dehydration † 1	12/293 (4.10%)	2/286 (0.70%)
Hypokalemia † 1	12/293 (4.10%)	2/286 (0.70%)
Hyperuricemia † 1	5/293 (1.71%)	7/286 (2.45%)
Hyponatremia † 1	4/293 (1.37%)	2/286 (0.70%)
Hyperkalemia † 1	3/293 (1.02%)	3/286 (1.05%)
Hypoalbuminemia † 1	3/293 (1.02%)	2/286 (0.70%)
Hypocalcemia † 1	3/293 (1.02%)	2/286 (0.70%)
Hypernatremia † 1	2/293 (0.68%)	3/286 (1.05%)
Hypoglycemia † 1	2/293 (0.68%)	2/286 (0.70%)
Hypercholesterolemia † 1	2/293 (0.68%)	0/286 (0.00%)
Diabetes mellitus † 1	0/293 (0.00%)	1/286 (0.35%)
Fluid overload † 1	0/293 (0.00%)	1/286 (0.35%)
Hyperchloremia † 1	0/293 (0.00%)	1/286 (0.35%)
Hyperphagia † 1	0/293 (0.00%)	1/286 (0.35%)
Hyperproteinemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hypomagnesemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hypophosphatemia † 1	1/293 (0.34%)	0/286 (0.00%)
Hypoproteinemia † 1	0/293 (0.00%)	1/286 (0.35%)
Hypovolemia † 1	1/293 (0.34%)	0/286 (0.00%)
Tumor lysis syndrome † 1	1/293 (0.34%)	0/286 (0.00%)
Tetany † 1	1/293 (0.34%)	0/286 (0.00%)
Musculoskeletal and connective tissue disorders
Myalgia † 1	94/293 (32.08%)	74/286 (25.87%)
Arthralgia † 1	70/293 (23.89%)	58/286 (20.28%)
Pain in extremity † 1	50/293 (17.06%)	50/286 (17.48%)
Bone pain † 1	34/293 (11.60%)	32/286 (11.19%)
Back pain † 1	26/293 (8.87%)	29/286 (10.14%)
Musculoskeletal pain † 1	23/293 (7.85%)	27/286 (9.44%)
Musculoskeletal chest pain † 1	3/293 (1.02%)	12/286 (4.20%)
Muscular weakness † 1	8/293 (2.73%)	4/286 (1.40%)
Neck pain † 1	6/293 (2.05%)	4/286 (1.40%)
Muscle spasms † 1	4/293 (1.37%)	5/286 (1.75%)
Groin pain † 1	2/293 (0.68%)	2/286 (0.70%)
Musculoskeletal discomfort † 1	2/293 (0.68%)	2/286 (0.70%)
Musculoskeletal stiffness † 1	2/293 (0.68%)	1/286 (0.35%)
Arthritis † 1	0/293 (0.00%)	2/286 (0.70%)
Flank pain † 1	1/293 (0.34%)	1/286 (0.35%)
Pain in jaw † 1	1/293 (0.34%)	1/286 (0.35%)
Pathological fracture † 1	1/293 (0.34%)	1/286 (0.35%)
Intervertebral disc disorder † 1	0/293 (0.00%)	1/286 (0.35%)
Joint effusion † 1	1/293 (0.34%)	0/286 (0.00%)
Joint swelling † 1	0/293 (0.00%)	1/286 (0.35%)
Myopathy † 1	0/293 (0.00%)	1/286 (0.35%)
Myositis † 1	0/293 (0.00%)	1/286 (0.35%)
Nodule on extremity † 1	0/293 (0.00%)	1/286 (0.35%)
Osteoporosis † 1	0/293 (0.00%)	1/286 (0.35%)
Sensation of heaviness † 1	0/293 (0.00%)	1/286 (0.35%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain † 1	2/293 (0.68%)	5/286 (1.75%)
Breast cancer † 1	0/293 (0.00%)	1/286 (0.35%)
Hemangioma † 1	0/293 (0.00%)	1/286 (0.35%)
Metastases to central nervous system † 1	1/293 (0.34%)	0/286 (0.00%)
Metastases to liver † 1	1/293 (0.34%)	0/286 (0.00%)
Pyogenic granuloma † 1	1/293 (0.34%)	0/286 (0.00%)
Salivary gland adenoma † 1	1/293 (0.34%)	0/286 (0.00%)
Squamous cell carcinoma † 1	1/293 (0.34%)	0/286 (0.00%)
Tumor hemorrhage † 1	1/293 (0.34%)	0/286 (0.00%)
Uterine leiomyoma † 1	1/293 (0.34%)	0/286 (0.00%)
Nervous system disorders
Peripheral sensory neuropathy † 1	48/293 (16.38%)	54/286 (18.88%)
Paraesthesia † 1	43/293 (14.68%)	42/286 (14.69%)
Headache † 1	32/293 (10.92%)	30/286 (10.49%)
Neuropathy peripheral † 1	54/293 (18.43%)	32/286 (11.19%)
Dysgeusia † 1	12/293 (4.10%)	11/286 (3.85%)
Dizziness † 1	13/293 (4.44%)	9/286 (3.15%)
Hypoaesthesia † 1	11/293 (3.75%)	10/286 (3.50%)
Polyneuropathy † 1	9/293 (3.07%)	3/286 (1.05%)
Peripheral motor neuropathy † 1	8/293 (2.73%)	4/286 (1.40%)
Neuralgia † 1	3/293 (1.02%)	4/286 (1.40%)
Memory impairment † 1	3/293 (1.02%)	3/286 (1.05%)
Syncope † 1	3/293 (1.02%)	2/286 (0.70%)
Convulsion † 1	2/293 (0.68%)	1/286 (0.35%)
Neurotoxicity † 1	1/293 (0.34%)	2/286 (0.70%)
Somnolence † 1	2/293 (0.68%)	1/286 (0.35%)
Tremor † 1	1/293 (0.34%)	2/286 (0.70%)
Cerebral infarction † 1	1/293 (0.34%)	1/286 (0.35%)
Disturbance in attention † 1	1/293 (0.34%)	1/286 (0.35%)
Hemiplegia † 1	1/293 (0.34%)	1/286 (0.35%)
Migraine † 1	1/293 (0.34%)	1/286 (0.35%)
Restless legs syndrome † 1	2/293 (0.68%)	0/286 (0.00%)
Sinus headache † 1	1/293 (0.34%)	1/286 (0.35%)
Aphasia † 1	1/293 (0.34%)	0/286 (0.00%)
Aphonia † 1	1/293 (0.34%)	0/286 (0.00%)
Brain edema † 1	1/293 (0.34%)	0/286 (0.00%)
Carpal tunnel syndrome † 1	0/293 (0.00%)	1/286 (0.35%)
Cerebrovascular disorder † 1	1/293 (0.34%)	0/286 (0.00%)
Coma hepatic † 1	0/293 (0.00%)	1/286 (0.35%)
Convulsions local † 1	0/293 (0.00%)	1/286 (0.35%)
Depressed level of consiousness † 1	0/293 (0.00%)	1/286 (0.35%)
Dysaesthesia † 1	1/293 (0.34%)	0/286 (0.00%)
Epilepsy † 1	0/293 (0.00%)	1/286 (0.35%)
Facial palsy † 1	0/293 (0.00%)	1/286 (0.35%)
Hyperaesthesia † 1	0/293 (0.00%)	1/286 (0.35%)
Hypersomnia † 1	1/293 (0.34%)	0/286 (0.00%)
Hyporeflexia † 1	0/293 (0.00%)	1/286 (0.35%)
Intracranial pressure increased † 1	1/293 (0.34%)	0/286 (0.00%)
Lethargy † 1	1/293 (0.34%)	0/286 (0.00%)
Loss of consciousness † 1	1/293 (0.34%)	0/286 (0.00%)
Lumbar radiculopathy † 1	0/293 (0.00%)	1/286 (0.35%)
Mental impairment † 1	1/293 (0.34%)	0/286 (0.00%)
Motor dysfunction † 1	1/293 (0.34%)	0/286 (0.00%)
Neuritis † 1	0/293 (0.00%)	1/286 (0.35%)
Paraparesis † 1	0/293 (0.00%)	1/286 (0.35%)
Parosmia † 1	1/293 (0.34%)	0/286 (0.00%)
Peripheral sensorimotor neurophathy † 1	0/293 (0.00%)	1/286 (0.35%)
Sciatica † 1	0/293 (0.00%)	1/286 (0.35%)
Sensory loss † 1	1/293 (0.34%)	0/286 (0.00%)
Psychiatric disorders
Insomnia † 1	34/293 (11.60%)	29/286 (10.14%)
Anxiety † 1	13/293 (4.44%)	13/286 (4.55%)
Depression † 1	10/293 (3.41%)	13/286 (4.55%)
Depressed mood † 1	4/293 (1.37%)	4/286 (1.40%)
Confusional state † 1	2/293 (0.68%)	3/286 (1.05%)
Restlessness † 1	1/293 (0.34%)	2/286 (0.70%)
Hallucination † 1	1/293 (0.34%)	1/286 (0.35%)
Mood altered † 1	2/293 (0.68%)	0/286 (0.00%)
Eating disorder † 1	1/293 (0.34%)	0/286 (0.00%)
Emotional distress † 1	0/293 (0.00%)	1/286 (0.35%)
Mental status changes † 1	0/293 (0.00%)	1/286 (0.35%)
Nervousness † 1	1/293 (0.34%)	0/286 (0.00%)
Panic attack † 1	1/293 (0.34%)	0/286 (0.00%)
Personality change † 1	1/293 (0.34%)	0/286 (0.00%)
Personality disorder † 1	1/293 (0.34%)	0/286 (0.00%)
Psychotic disorder † 1	0/293 (0.00%)	1/286 (0.35%)
Suicidal ideation † 1	1/293 (0.34%)	0/286 (0.00%)
Renal and urinary disorders
Dysuria † 1	6/293 (2.05%)	2/286 (0.70%)
Hematuria † 1	3/293 (1.02%)	0/286 (0.00%)
Urinary incontinence † 1	1/293 (0.34%)	3/286 (1.05%)
Hydronephrosis † 1	1/293 (0.34%)	2/286 (0.70%)
Polyuria † 1	2/293 (0.68%)	0/286 (0.00%)
Enuresis † 1	0/293 (0.00%)	1/286 (0.35%)
Micturition disorder † 1	1/293 (0.34%)	0/286 (0.00%)
Pollakiuria † 1	0/293 (0.00%)	1/286 (0.35%)
Renal colic † 1	1/293 (0.34%)	0/286 (0.00%)
Renal failure acute † 1	1/293 (0.34%)	0/286 (0.00%)
Urinary retention † 1	0/293 (0.00%)	1/286 (0.35%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	33/293 (11.26%)	42/286 (14.69%)
Dyspnoea † 1	29/293 (9.90%)	28/286 (9.79%)
Oropharyngeal pain † 1	12/293 (4.10%)	10/286 (3.50%)
Epistaxis † 1	13/293 (4.44%)	4/286 (1.40%)
Dysphonia † 1	8/293 (2.73%)	6/286 (2.10%)
Productive cough † 1	5/293 (1.71%)	2/286 (0.70%)
Dyspnoea exertional † 1	3/293 (1.02%)	1/286 (0.35%)
Rhinitis allergic † 1	2/293 (0.68%)	2/286 (0.70%)
Hemoptysis † 1	0/293 (0.00%)	3/286 (1.05%)
Nasal congestion † 1	1/293 (0.34%)	1/286 (0.35%)
Nasal dryness † 1	2/293 (0.68%)	1/286 (0.35%)
Wheezing † 1	1/293 (0.34%)	2/286 (0.70%)
Asthma † 1	1/293 (0.34%)	1/286 (0.35%)
Bronchospasm † 1	1/293 (0.34%)	1/286 (0.35%)
Hypoxia † 1	0/293 (0.00%)	3/286 (1.05%)
Increased upper airway secretion † 1	1/293 (0.34%)	1/286 (0.35%)
Nasal inflammation † 1	2/293 (0.68%)	0/286 (0.00%)
Pharyngeal erythema † 1	1/293 (0.34%)	1/286 (0.35%)
Pleural effusion † 1	1/293 (0.34%)	1/286 (0.35%)
Pulmonary embolism † 1	2/293 (0.68%)	0/286 (0.00%)
Pleuritic pain † 1	1/293 (0.34%)	0/286 (0.00%)
Atelectasis † 1	0/293 (0.00%)	1/286 (0.35%)
Bronchostenosis † 1	0/293 (0.00%)	1/286 (0.35%)
Hemothorax † 1	0/293 (0.00%)	1/286 (0.35%)
Lung infiltration † 1	0/293 (0.00%)	1/286 (0.35%)
Nasal discomfort † 1	1/293 (0.34%)	0/286 (0.00%)
Nasal ulcer † 1	0/293 (0.00%)	1/286 (0.35%)
Pain respiration † 1	1/293 (0.34%)	0/286 (0.00%)
Pleural fibrosis † 1	1/293 (0.34%)	0/286 (0.00%)
Pneumonitis † 1	0/293 (0.00%)	1/286 (0.35%)
Pulmonary hemorrhage † 1	1/293 (0.34%)	0/286 (0.00%)
Pulmonary edema † 1	1/293 (0.34%)	0/286 (0.00%)
Rales † 1	1/293 (0.34%)	0/286 (0.00%)
Respiratory disorder † 1	1/293 (0.34%)	0/286 (0.00%)
Rhinorrhoea † 1	1/293 (0.34%)	0/286 (0.00%)
Sinus congestion † 1	0/293 (0.00%)	1/286 (0.35%)
Sputum discoloured † 1	1/293 (0.34%)	0/286 (0.00%)
Upper airway obstruction † 1	0/293 (0.00%)	1/286 (0.35%)
Skin and subcutaneous tissue disorders
Alopecia † 1	153/293 (52.22%)	183/286 (63.99%)
Rash † 1	145/293 (49.49%)	66/286 (23.08%)
Pruritus † 1	46/293 (15.70%)	37/286 (12.94%)
Dry skin † 1	13/293 (4.44%)	8/286 (2.80%)
Nail disorder † 1	8/293 (2.73%)	5/286 (1.75%)
Pain of skin † 1	4/293 (1.37%)	4/286 (1.40%)
Skin hyperpigmentation † 1	7/293 (2.39%)	1/286 (0.35%)
Hyperhidrosis † 1	3/293 (1.02%)	3/286 (1.05%)
Rash generalized † 1	3/293 (1.02%)	2/286 (0.70%)
Palmar-plantar erythrodysaesthesia syndrome † 1	5/293 (1.71%)	1/286 (0.35%)
Urticaria † 1	2/293 (0.68%)	3/286 (1.05%)
Ecchymosis † 1	1/293 (0.34%)	2/286 (0.70%)
Rash erythematous † 1	2/293 (0.68%)	1/286 (0.35%)
Dermatitis allergic † 1	2/293 (0.68%)	1/286 (0.35%)
Nail discoloration † 1	1/293 (0.34%)	1/286 (0.35%)
Night sweats † 1	1/293 (0.34%)	1/286 (0.35%)
Pruritus generalized † 1	0/293 (0.00%)	2/286 (0.70%)
Skin exfoliation † 1	0/293 (0.00%)	2/286 (0.70%)
Skin fissures † 1	1/293 (0.34%)	1/286 (0.35%)
Blister † 1	0/293 (0.00%)	1/286 (0.35%)
Butterfly rash † 1	0/293 (0.00%)	1/286 (0.35%)
Cold sweat † 1	0/293 (0.00%)	1/286 (0.35%)
Erythema multiforme † 1	1/293 (0.34%)	0/286 (0.00%)
Hemorrhage subcutaneous † 1	0/293 (0.00%)	1/286 (0.35%)
Hair growth abnormal † 1	1/293 (0.34%)	0/286 (0.00%)
Hirsutism † 1	1/293 (0.34%)	0/286 (0.00%)
Hypertrichosis † 1	1/293 (0.34%)	0/286 (0.00%)
Hypoaesthesia facial † 1	1/293 (0.34%)	0/286 (0.00%)
Ingrowing nail † 1	1/293 (0.34%)	0/286 (0.00%)
Intertrigo † 1	0/293 (0.00%)	1/286 (0.35%)
Madarosis † 1	0/293 (0.00%)	1/286 (0.35%)
Onychalgia † 1	1/293 (0.34%)	0/286 (0.00%)
Onycholysis † 1	1/293 (0.34%)	0/286 (0.00%)
Periorbital edema † 1	1/293 (0.34%)	0/286 (0.00%)
Rosacea † 1	1/293 (0.34%)	0/286 (0.00%)
Skin chapped † 1	1/293 (0.34%)	0/286 (0.00%)
Skin discomfort † 1	1/293 (0.34%)	0/286 (0.00%)
Skin disorder † 1	0/293 (0.00%)	1/286 (0.35%)
Skin lesion † 1	1/293 (0.34%)	0/286 (0.00%)
Swelling face † 1	1/293 (0.34%)	0/286 (0.00%)
Social circumstances
Immobile † 1	0/293 (0.00%)	1/286 (0.35%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title: GSK Response Center

Organization: GlaxoSmithKline

Phone: 866-435-7343

Publications:

Tenori L, Oakman C, Claudino WM, Bernini P, Cappadona S, Nepi S, Biganzoli L, Arbushites MC, Luchinat C, Bertini I, Di Leo A. Exploration of serum metabolomic profiles and outcomes in women with metastatic breast cancer: a pilot study. Mol Oncol. 2012 Aug;6(4):437-44. doi: 10.1016/j.molonc.2012.05.003. Epub 2012 Jun 1.

Finn RS, Press MF, Dering J, Arbushites M, Koehler M, Oliva C, Williams LS, Di Leo A. Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib or placebo as first-line treatment in HER2-negative or unknown metastatic breast cancer. J Clin Oncol. 2009 Aug 20;27(24):3908-15. doi: 10.1200/JCO.2008.18.1925. Epub 2009 Jul 20.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sherrill B, Di Leo A, Amonkar MM, Wu Y, Zvirbule Z, Aziz Z, Bines J, Gomez HL. Quality-of-life and quality-adjusted survival (Q-TWiST) in patients receiving lapatinib in combination with paclitaxel as first-line treatment for metastatic breast cancer. Curr Med Res Opin. 2010 Apr;26(4):767-75. doi: 10.1185/03007991003590860.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00075270 History of Changes
Obsolete Identifiers:	NCT00085046
Other Study ID Numbers:	EGF30001
First Submitted:	January 7, 2004
First Posted:	January 9, 2004
Results First Submitted:	March 14, 2013
Results First Posted:	March 31, 2014
Last Update Posted:	May 6, 2015