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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00075270
First received: January 7, 2004
Last updated: February 13, 2014
Last verified: December 2013
Results First Received: March 14, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Neoplasms, Breast
Interventions: Drug: Paclitaxel
Drug: GW572016 (Lapatinib)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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]).

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Participant Flow:   Overall Study
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
STARTED     291     288  
Missing     26 [1]   13 [1]
COMPLETED     5     4  
NOT COMPLETED     286     284  
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
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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 Total of all reporting groups

Baseline Measures
    Lapatinib With Paclitaxel     Placebo With Paclitaxel     Total  
Number of Participants  
[units: participants]
  291     288     579  
Age  
[units: Years]
Mean ± Standard Deviation
  51.3  ± 10.45     52.4  ± 10.98     51.8  ± 10.72  
Gender  
[units: Participants]
     
Female     291     288     579  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
White     190     182     372  
Black     10     10     20  
Asian     30     35     65  
American Hispanic     54     53     107  
Unknown     7     8     15  



  Outcome Measures
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1.  Primary:   Time to Progression as Evaluated by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

Measure Type Primary
Measure Title Time to Progression as Evaluated by the Investigator
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all randomized participants who had received at least one dose of randomized therapy (lapatinib or placebo)

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Time to Progression as Evaluated by the Investigator  
[units: weeks]
Median ( Inter-Quartile Range )
  29.0  
  ( 13.9 to 46.9 )  
  22.9  
  ( 12.0 to 38.3 )  


Statistical Analysis 1 for Time to Progression as Evaluated by the Investigator
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.142
Hazard Ratio, log [4] 0.87
95% Confidence Interval ( 0.72 to 1.05 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value from stratified log-rank test, stratifying for stage of disease and site of disease at screening
[4] Other relevant estimation information:
  The estimate of the treatment hazard ratio is based on the log-rank test.



2.  Primary:   Time to Progression as Evaluated by the Independent Review Committee (IRC)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

Measure Type Primary
Measure Title Time to Progression as Evaluated by the Independent Review Committee (IRC)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Time to Progression as Evaluated by the Independent Review Committee (IRC)  
[units: weeks]
Median ( Inter-Quartile Range )
  33.7  
  ( 18.7 to 69.1 )  
  26.1  
  ( 12.9 to 57.1 )  


Statistical Analysis 1 for Time to Progression as Evaluated by the Independent Review Committee (IRC)
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.094
Hazard Ratio, log [4] 0.82
95% Confidence Interval ( 0.65 to 1.04 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value from stratified log-rank test, stratifying for stage of disease and site of disease at screening
[4] Other relevant estimation information:
  The estimate of the treatment hazard ratio was based on the log-rank test.



3.  Secondary:   Number of Participants With Tumor Response as Evaluated by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

Measure Type Secondary
Measure Title Number of Participants With Tumor Response as Evaluated by the Investigator
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Number of Participants With Tumor Response as Evaluated by the Investigator  
[units: participants]
   
CR     14     6  
PR     88     67  

No statistical analysis provided for Number of Participants With Tumor Response as Evaluated by the Investigator



4.  Secondary:   Number of Participants With Tumor Response as Evaluated by the Independent Review Committee   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

Measure Type Secondary
Measure Title Number of Participants With Tumor Response as Evaluated by the Independent Review Committee
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Number of Participants With Tumor Response as Evaluated by the Independent Review Committee  
[units: participants]
   
CR     1     1  
PR     77     53  

No statistical analysis provided for Number of Participants With Tumor Response as Evaluated by the Independent Review Committee



5.  Secondary:   Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

Measure Type Secondary
Measure Title Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator  
[units: Percentage of participants]
  40.5     31.9  

No statistical analysis provided for Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator



6.  Secondary:   Number of Participants With a Response of CR or PR by the Indicated Study Week   [ Time Frame: Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72 ]

Measure Type Secondary
Measure Title Number of Participants With a Response of CR or PR by the Indicated Study Week
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Number of Participants With a Response of CR or PR by the Indicated Study Week  
[units: 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  

No statistical analysis provided for Number of Participants With a Response of CR or PR by the Indicated Study Week



7.  Secondary:   Duration of Response (DOR)   [ 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) ]

Measure Type Secondary
Measure Title Duration of Response (DOR)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population. Only participants who had a CR or PR were evaluated.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  102     73  
Duration of Response (DOR)  
[units: weeks]
Median ( Inter-Quartile Range )
  28.3  
  ( 22.3 to 50.0 )  
  27.1  
  ( 18.1 to 46.3 )  

No statistical analysis provided for Duration of Response (DOR)



8.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

Measure Type Secondary
Measure Title Progression-Free Survival (PFS)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Progression-Free Survival (PFS)  
[units: weeks]
Median ( 95% Confidence Interval )
  25.1  
  ( 21.9 to 32.1 )  
  22.6  
  ( 21.0 to 25.4 )  

No statistical analysis provided for Progression-Free Survival (PFS)



9.  Secondary:   Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

Measure Type Secondary
Measure Title Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)  
[units: participants]
  133     153  

No statistical analysis provided for Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)



10.  Secondary:   Overall Survival   [ Time Frame: Randomization until the date of death due to any cause (average of 24 months) ]

Measure Type Secondary
Measure Title Overall Survival
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Overall Survival  
[units: months]
Median ( 95% Confidence Interval )
  23.82  
  ( 19.88 to 26.18 )  
  20.17  
  ( 17.84 to 23.92 )  

No statistical analysis provided for Overall Survival



11.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

Measure Type Secondary
Measure Title Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  208     230  
Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores  
[units: Scores on a scale]
Mean ± Standard Deviation
   
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  

No statistical analysis provided for Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores



12.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

Measure Type Secondary
Measure Title Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  213     232  
Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores  
[units: Scores on a scale]
Mean ± Standard Deviation
   
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  

No statistical analysis provided for Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores



13.  Secondary:   Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

Measure Type Secondary
Measure Title Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  208     232  
Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores  
[units: Scores on a scale]
Mean ± Standard Deviation
   
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  

No statistical analysis provided for Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores



14.  Secondary:   Number of Participants With the Indicated ErbB2 Status at Baseline   [ Time Frame: Baseline ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated ErbB2 Status at Baseline
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Number of Participants With the Indicated ErbB2 Status at Baseline  
[units: participants]
   
Positive     52     39  
Negative     199     202  
Assay not done     40     47  

No statistical analysis provided for Number of Participants With the Indicated ErbB2 Status at Baseline



15.  Secondary:   ErbB2 Ratio   [ Time Frame: Baseline ]

Measure Type Secondary
Measure Title ErbB2 Ratio
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  220     200  
ErbB2 Ratio  
[units: ratio of signals]
Mean ± Standard Deviation
  2.23  ± 2.301     2.14  ± 2.214  

No statistical analysis provided for ErbB2 Ratio



16.  Secondary:   Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening   [ Time Frame: Screening (Day -1) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening  
[units: participants]
   
0     139     139  
1+     50     51  
2+     15     22  
3+     40     28  
Assay not done     47     48  

No statistical analysis provided for Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening



17.  Secondary:   Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results   [ Time Frame: Baseline ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  291     288  
Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results  
[units: participants]
   
Amplified     45     35  
Non-amplified     175     165  
Assay not done     71     88  

No statistical analysis provided for Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results



18.  Secondary:   Serum ErbB1 Concentration   [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

Measure Type Secondary
Measure Title Serum ErbB1 Concentration
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  269     265  
Serum ErbB1 Concentration  
[units: Nanograms per milliliter (ng/mL)]
Mean ± Standard Deviation
   
Screening, n=269, 265     58.6  ± 20.30     59.5  ± 44.20  
Withdrawal, n=145, 157     59.0  ± 30.22     61.5  ± 16.74  

No statistical analysis provided for Serum ErbB1 Concentration



19.  Secondary:   Serum ErbB2 Concentration   [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

Measure Type Secondary
Measure Title Serum ErbB2 Concentration
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  270     265  
Serum ErbB2 Concentration  
[units: ng/mL]
Mean ± Standard Deviation
   
Screening, n=270, 265     37.67  ± 95.883     36.19  ± 87.629  
Withdrawal, n=145, 158     37.31  ± 98.257     39.95  ± 96.327  

No statistical analysis provided for Serum ErbB2 Concentration



20.  Secondary:   Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4   [ Time Frame: Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks) ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Lapatinib With Paclitaxel 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.
Placebo With Paclitaxel 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.

Measured Values
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Number of Participants Analyzed  
[units: participants]
  293     286  
Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4  
[units: 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  

No statistical analysis provided for Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00075270     History of Changes
Obsolete Identifiers: NCT00085046
Other Study ID Numbers: EGF30001
Study First Received: January 7, 2004
Results First Received: March 14, 2013
Last Updated: February 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration