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Study Comparing GW572016 And Letrozole Versus Letrozole In Subjects With Advanced Or Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00073528
Recruitment Status : Completed
First Posted : November 26, 2003
Results First Posted : May 17, 2012
Last Update Posted : October 4, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Neoplasms, Breast
Interventions Drug: Lapatinib (GW572016)
Drug: Letrozole
Enrollment 1285
Recruitment Details  
Pre-assignment Details At the time of data cut off for this analysis there were still participants on study (ongoing). The maximum treatment period was up to 46 months at the time of the analyses of data presented in this results summary.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months. Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Period Title: Overall Study
Started 644 642
Ongoing 349 [1] 344 [1]
Completed 0 0
Not Completed 644 642
Reason Not Completed
Withdrawal by Subject             34             29
Lost to Follow-up             26             22
Protocol Violation             3             5
Death             229             238
Mastectomy Intervention             1             0
Randomized in Error; Not Treated             2             0
Progressive Disease             0             1
Participant Was Unblinded             0             1
Enrolled in Error             0             1
Non-compliance             0             1
Ongoing             349             344
[1]
These participants are still on study and do not yet have end of study data available.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg Total
Hide Arm/Group Description Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months. Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months. Total of all reporting groups
Overall Number of Baseline Participants 644 642 1286
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 644 participants 642 participants 1286 participants
63.3  (9.95) 62.8  (9.70) 63.1  (9.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 644 participants 642 participants 1286 participants
Female
644
 100.0%
642
 100.0%
1286
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 644 participants 642 participants 1286 participants
White
557
  86.5%
529
  82.4%
1086
  84.4%
Black
10
   1.6%
17
   2.6%
27
   2.1%
Asian
30
   4.7%
30
   4.7%
60
   4.7%
American Hispanic
44
   6.8%
57
   8.9%
101
   7.9%
Other
3
   0.5%
9
   1.4%
12
   0.9%
1.Primary Outcome
Title Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Her3 as Assessed by the Investigator
Hide Description PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. The date of documented PD is defined as the date of radiological PD as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0), PD is defined as a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Time Frame From the date of randomization until the date of the first documented progression or date of death from any cause, whichever came first, assessed for up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population: all randomized participants who had documented amplification of baseline HER2 by fluorescence in situ hybridization (FISH) (=>2.0) or 3+ immunohistochemistry (IHC) (or 2+ IHC and FISH +) in archived tumor tissue regardless of whether or not study treatment had been received.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 108 111
Measure Type: Number
Unit of Measure: participants
89 88
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letrozole 2.5 mg Plus Placebo, Letrozole 2.5 mg Plus Lapatinib 1500 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments p-value is from stratified log-rank test, stratifying for site of disease and time since prior adjuvant endocrine therapy at screening
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.53 to 0.96
Estimation Comments The estimate of the treatment Hazard Ratio wase based on the log-rank test.
2.Primary Outcome
Title Progression Free Survival (PFS) of Participants in the HER2-Positive Population as Assessed by the Investigator
Hide Description PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Time Frame From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants who experienced disease progression or died during their participation in the study were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 89 88
Median (95% Confidence Interval)
Unit of Measure: weeks
13.0
(12.0 to 23.7)
35.4
(24.1 to 39.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Letrozole 2.5 mg Plus Placebo, Letrozole 2.5 mg Plus Lapatinib 1500 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments p-value is from stratified log-rank test, stratifying for site of disease and time since prior adjuvant endocrine therapy at screening
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.53 to 0.96
Estimation Comments The estimate of the treatment Hazard Ratio was based on the log-rank test.
3.Secondary Outcome
Title Number of Participants With PFS in the Intent-To-Treat (ITT) Population as Assessed by the Investigator
Hide Description PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Time Frame From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: all randomized participants, regardless of whether or not study treatment had been received. The ITT Population included the HER2-Positive Population, the HER2-Negative Population, and the HER2-Missing Population.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: participants
476 413
4.Secondary Outcome
Title PFS in Participants in the ITT Population as Assessed by the Investigator
Hide Description PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Time Frame From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who experienced disease progression or died during their participation in the study were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 476 413
Median (95% Confidence Interval)
Unit of Measure: weeks
47.0
(36.9 to 50.9)
51.7
(47.6 to 59.6)
5.Secondary Outcome
Title Overall Survival in the HER2-Positive Population
Hide Description Overall survival was defined as the time from randomization until death due to any cause.
Time Frame From date of randomization until date of death due to any cause, assessed up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants who died during the study due to any cause were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 54 50
Median (95% Confidence Interval)
Unit of Measure: weeks
140.3
(92.1 to 159.4)
144.7 [1] 
(95.6 to NA)
[1]
Too few events occurred to fully define the confidence interval.
6.Secondary Outcome
Title Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator
Hide Description OR is defined as the percentage of participants achieving either a confirmed complete response (CR) or partial response (PR). Response was assessed via Response Evaluation criteria in Solid Tumors (RECIST). The percentage of participants with response was calculated by using the formula: 100 * (number of participants with CR + number of participants with PR)/total number of participants. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 108 111
Measure Type: Number
Unit of Measure: percentage of participants
14.8 27.9
7.Secondary Outcome
Title Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator
Hide Description Participants were stratified based on site of disease at screening (SDS) (soft tissue or visceral or bone-only disease) and prior adjuvant endocrine therapy (PAET) (discontinuation interval [DI] =>6 months or DI <6 months). OR is defined as the number of participants achieving either a confirmed CR or PR. Response was assessed via RECIST. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. DI is defined as the time period from stopping the PEAT to the randomization date.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants with measurable disease, including bone scans, were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 75 93
Measure Type: Number
Unit of Measure: participants
SDS, Soft tissue or visceral; n=75, 93 14 31
SDS, Bone-only disease; n=0, 0 0 0
PAET, DI =>6 months; n=53, 61 12 24
PAET, DI <6 months; n=22, 32 2 7
8.Secondary Outcome
Title Clinical Benefit (CB) in the HER2-Positive Population as Assessed by the Investigator
Hide Description CB is defined as the percentage of participants with evidence of confirmed CR, PR, or stable disease (SD) for at least 6 months. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the baseline measurement.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 108 111
Measure Type: Number
Unit of Measure: percentage of participants
28.7 47.7
9.Secondary Outcome
Title Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator.
Hide Description CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum LD since the baseline measurement. The best overall response is defined as the best response recorded from the start of treatment until disease progression/recurrence. PD: presence of target lesions, non-target lesions, and/or new lesions.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 108 111
Measure Type: Number
Unit of Measure: participants
CR 4 5
PR 12 26
SD 35 44
PD 49 30
Unknown 8 6
10.Secondary Outcome
Title Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator.
Hide Description CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum LD since the baseline measurement. The best overall response is defined as the best response recorded from the start of treatment until disease progression/recurrence. PD: presence of target lesions, non-target lesions, and/or new lesions.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: participants
CR 26 28
PR 153 168
SD 243 280
PD 174 113
Unknown 48 53
11.Secondary Outcome
Title Number of Participants With the Indicated Time to Response for CR or PR in the HER2-Positive Population as Assessed by the Investigator
Hide Description Time to response is defined as the time from randomization until the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sume of the LD of target lesions, taking as reference the baseline sum LD) (whichever status was recorded first). The assessments of CR or PR required confirmation using bone scans.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants with CR or PR were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 16 31
Measure Type: Number
Unit of Measure: participants
Week 12 11 23
Week 16 1 3
Week 24 or longer 4 5
12.Secondary Outcome
Title Duration of Response for the Participants With CR or PR in the HER2-Positive Population as Assessed by the Investigator
Hide Description Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD) until the first documented sign of disease progression or death due to any cause. The assessments of CR or PR required confirmation using bone scans.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants with CR or PR were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 16 31
Median (Inter-Quartile Range)
Unit of Measure: weeks
84.4 [1] 
(29.1 to NA)
47.4
(25.1 to 108.0)
[1]
Too few events occurred to fully define the confidence interval.
13.Secondary Outcome
Title Number of Participants With Evidence of Brain Metastases in the HER2-Positive Population
Hide Description The confirmation criteria for the evidence of brain metastases was the incidence of lesions occurring within any part of the central nervous system (CNS) as evidenced by radiological scans. Metastases are defined as the spread of cancer from one part of the body to another.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 108 111
Measure Type: Number
Unit of Measure: participants
2 1
14.Secondary Outcome
Title Time to Progression (TTP) for the HER2-Positive Population as Assessed by the Investigator
Hide Description TTP is defined as the interval between the date of randomization and the earliest date of disease progression or death due to breast cancer. Disease progression was based on the assessments by the Investigator.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants who experienced disease progression or died due to breast cancer were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 89 87
Median (95% Confidence Interval)
Unit of Measure: weeks
13.0
(12.0 to 23.7)
35.4
(24.1 to 39.4)
15.Secondary Outcome
Title Overall Survival in the ITT Population
Hide Description Overall survival was defined as the time from randomization until death due to any cause.
Time Frame From date of randomization until date of death due to any cause, assessed up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who died during the study due to any cause were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 234 240
Median (95% Confidence Interval)
Unit of Measure: weeks
176.3
(156.1 to 189.7)
170.9
(157.7 to 196.3)
16.Secondary Outcome
Title Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator
Hide Description OR is defined as the percentage of participants achieving either a confirmed complete response (CR) or partial response (PR). Response was assessed via Response Evaluation criteria in Solid Tumors (RECIST). The percentage of participants with response was calculated by using the formula: 100 * (number of participants with CR + number of participants with PR)/total number of participants. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who achieved either a confirmed CR or PR were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: percentage of participants
27.8 30.5
17.Secondary Outcome
Title Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator
Hide Description Participants were stratified based on site of disease at screening (SDS) (soft tissue or visceral or bone-only disease) and prior adjuvant endocrine therapy (PAET) (discontinuation interval [DI] =>6 months or DI <6 months). OR is defined as the number of participants achieving either a confirmed CR or PR. Response was assessed via RECIST. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. DI is defined as the time period from stopping the PEAT and the randomization date.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with some measurable disease were assessed. Response with bone scan confirmation was required. Participants with bone-only disease were excluded from the analysis because bone-only disease is non-measurable only per RECIST 1.0.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 486 480
Measure Type: Number
Unit of Measure: participants
SDS, Soft tissue or visceral; n=486, 480 170 190
PAET, DI =>6 months; n=376, 381 151 168
PAET, DI <6 months; n=110, 99 19 22
18.Secondary Outcome
Title Clinical Benefit (CB) in the ITT Population as Assessed by the Investigator
Hide Description CB is defined as the percentage of participants with evidence of confirmed CR, PR, or stable disease (SD) for at least 6 months. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the baseline measurement.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: percentage of participants
50.6 55.8
19.Secondary Outcome
Title Number of Participants With the Indicated Time to Response for CR or PR in the ITT Population as Assessed by the Investigator
Hide Description Time to response is defined as the time from randomization until the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sume of the LD of target lesions, taking as reference the baseline sum LD) (whichever status was recorded first). The assessments of CR or PR required confirmation using bone scans.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with CR or PR were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 179 196
Measure Type: Number
Unit of Measure: participants
Week 12 76 94
Week 16 21 18
Week 24 28 28
Week 28 17 14
Week 36 or longer 37 42
20.Secondary Outcome
Title Duration of Response for the Participants With CR or PR in the ITT Population as Assessed by the Investigator
Hide Description Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD) until the first documented sign of disease progression or death due to any cause. The assessments of CR or PR required confirmation using bone scans.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with CR or PR response were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 179 196
Median (Inter-Quartile Range)
Unit of Measure: weeks
72.6
(39.1 to 145.7)
60.1
(36.0 to 138.9)
21.Secondary Outcome
Title Number of Participants With Evidence of Brain Metastases From the ITT Population
Hide Description The confirmation criteria for the evidence of brain metastases was the incidence of lesions occurring within any part of the central nervous system (CNS) as evidenced by radiological scans. Metastases are defined as the spread of cancer from one part of the body to another.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: participants
4 6
22.Secondary Outcome
Title TTP for Participants From the ITT Population as Assessed by the Investigator
Hide Description TTP is defined as the interval between the date of randomization and the earliest date of disease progression or death due to breast cancer. Disease progression was based on the assessments by the Investigator.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who experienced disease progression or died due to breast cancer were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 469 409
Median (95% Confidence Interval)
Unit of Measure: weeks
47.0
(36.9 to 50.9)
51.7
(47.6 to 59.6)
23.Secondary Outcome
Title Number of Participants With the Indicated Adverse Events (AEs) Related to Study Treatment Reported in 10% or More Participants in Either Treatment Arm
Hide Description An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study treatment.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all randomized participants who had received at least 1 dose of study treatment, based on the actual treatment received if this differed from that to which the participant was randomized. All participants with any AE related to study treatment were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 343 548
Measure Type: Number
Unit of Measure: participants
Diarrhea 79 348
Rash 57 249
Nausea 69 129
Dry skin 19 69
Fatigue 46 70
Alopecia 33 64
Nail disorder 4 66
Pruritus 35 64
24.Secondary Outcome
Title Number of Participants With the Indicated Serious Adverse Events (SAEs) Related to Study Drug Reported by More Than One Participant in Either Treatment Arm
Hide Description An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants who experienced SAEs related to study drug that were reported by more than one participant in either treatment arm were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 27 54
Measure Type: Number
Unit of Measure: participants
Ejection fraction decreased 7 10
Diarrhea 1 5
Left ventricular dysfunction 0 4
Vomiting 3 3
Dehydration 1 3
Nausea 1 2
Asthenia 0 2
Hepatic function abnormal 0 2
Paronychia 0 2
Rash 0 2
Anorexia 2 1
Anemia 2 0
25.Secondary Outcome
Title Number of Participants Completing the Functional Assessment of Cancer Therapy-breast (FACT-B) Questionnaire at the Scheduled Visits
Hide Description Quality of Life (QOL) was assessed using the FACT-B questionnaire, which was a 37-item (27 general and 10 breast cancer-specific questions) self-reporting instrument consisting of 5 dimensions: physical-, social/family-, emotional-, functional-well being, and a breast cancer subscale. Higher scores on the FACT-B scales (each ranging from 0 [not at all] to 4 [very much]) indicate a higher QOL. The score is transformed for FACT-B and results in a total score ranging from 0 to 144. Complete: completing at least 1 question from FACT-B.
Time Frame Day 1 (baseline) visit; Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192 visits; conclusion/withdrawal visit
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: participants
Day 1, baseline 605 605
Week 12 460 476
Week 24 350 382
Week 36 291 294
Week 48 254 243
Week 60 199 183
Week 72 181 153
Week 84 144 119
Week 96 117 98
Week 108 80 62
Week 120 59 56
Week 132 43 43
Week 144 33 33
Week 156 22 21
Week 168 15 11
Week 180 11 5
Week 192 6 1
Conclusion/withdrawal 327 359
26.Secondary Outcome
Title Adjusted Mean Change From Baseline for the FACT-B Total Score Using Observed Data
Hide Description Quality of Life (QOL) was assessed using the FACT-B questionnaire, which is a 37-item (27 general and 10 breast cancer-specific questions) self-reporting instrument consisting of 5 dimensions: physical-, social/family-, emotional-, functional-well being, and a breast cancer subscale. Higher scores on the FACT-B scales indicate a higher QOL; each ranging from 0 (not at all) to 4 (very much). The score is transformed for FACT-B and results in a total score ranging from 0 to 144. The FACT-B is designed to measure multidimensional QOL in participants with breast cancer.
Time Frame Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants whose item response rate was greater than 80% were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 61 78
Mean (Standard Error)
Unit of Measure: scores on a scale
Week 12; n=57, 78 1.5  (1.88) 3.3  (1.60)
Week 24; n=36, 53 3.8  (2.20) 1.9  (1.80)
Week 36; n=23, 31 3.3  (2.87) 1.4  (2.46)
Week 48; n=22, 23 2.9  (2.91) 0.3  (2.84)
Conclusion/WD; n=61, 69 -9.4  (2.03) -9.0  (1.91)
27.Secondary Outcome
Title Adjusted Mean Change From Baseline for the Functional Assessment of Cancer Therapy-General (FACT-G) Score Using Observed Data
Hide Description FACT-G is a subscale of the FACT-B QOL questionnaire and consists of 27 questions grouped into 4 domains that measure a participant's physical, functional, social and family, and emotional well-being. FACT-G is assessed on a five-point Likert-type scale, with scores ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). The total score is calculated as the sum of the item scores on the subscale; the total ranges from 0 to 108, with higher score indicating a better quality of life.
Time Frame Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants whose item response rate was greater than 80% were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 63 79
Mean (Standard Error)
Unit of Measure: scores on a scale
Week 12; n=60, 79 1.6  (1.55) 1.5  (1.35)
Week 24; n=37, 54 2.2  (1.72) 0.6  (1.42)
Week 36; n=24, 33 2.6  (2.18) 0.9  (1.85)
Week 48; n=23, 25 2.0  (2.50) -0.9  (2.40)
Conclusion/WD; n=63, 71 -7.8  (1.62) -8.5  (1.53)
28.Secondary Outcome
Title Adjusted Mean Change From Baseline for the Trial Outcome Index (TOI) Score Using Observed Data
Hide Description The TOI score is the sum of the physical well-being, functional well-being, and breast cancer unweighted subscale scores. The total TOI score ranges from 0 to 92, with higher scores representing a better quality of life.
Time Frame Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants whose item response rate was greater than 80% were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 62 77
Mean (Standard Error)
Unit of Measure: scores on a scale
Week 12; n=59, 77 -0.3  (1.30) 2.7  (1.14)
Week 24, n=37, 52 3.9  (1.58) 2.0  (1.33)
Week 36; n=24, 28 3.3  (2.09) 0.8  (1.94)
Week 48; n=22, 23 2.2  (2.27) -0.7  (2.22)
Conclusion/WD; n=62, 67 -6.2  (1.56) -6.4  (1.50)
29.Secondary Outcome
Title Number of Participants Classified as QOL Responders Based on the FACT-B, FACT-G, and TOI Total Scores
Hide Description A minimally important difference (MID) is the smallest difference in a score for a measure of QOL that corresponds to a difference in function or clinical course. Responders are defined as participants with an MID => 8 for the FACT-B score, and an MID =>6 for the FACT-G and TOI scores.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Positive Population. Only those participants with a baseline score and at least one post-baseline score were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 87 99
Measure Type: Number
Unit of Measure: participants
FACT-B total, =>8 (MID upper bound), n=85, 98 29 33
FACT-G, =>6 (MID upper bound); n=87, 99 29 38
TOI, =>6 (MID upper bound); n=87, 97 29 33
30.Secondary Outcome
Title Number of Participants With Clinical Benefit Categorized by HER2 Fluorescence in Situ Hybridization (FISH) Status
Hide Description Clinical benefit: participants with CR, PR, or SD for =>6-month period. FISH testing measures the amount of the HER2 gene in each cell. This gene is responsible for the overproduction of the HER2 protein. FISH-positive: excessive amounts of the gene are present; FISH-negative: normal levels of the gene are present.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: participants
FISH status, Positive; n=96, 97 28 49
FISH status, Negative; n=412, 422 237 245
FISH status, missing; n=136, 123 61 64
31.Secondary Outcome
Title Number of Participants With Clinical Benefit Categorized by HER2 ImmunoHistoChemistry (IHC) Intensity
Hide Description IHC is a commonly used test to assess the amount of the HER2 receptor protein on the surface of the cancer cells. The IHC test results in a score of 0 to 3+, which indicates the amount of HER2 receptor protein on the cells in a sample of breast cancer tissue. Tissue scores of 0 to 1+ indicate HER2 negativity; scores of 2+ and 3+ indicate HER2 positivity. Clinical benefit is defined as participants with CR, PR, or SD for =>6-month period.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: participants
IHC Intensity 0, n=153, 177 74 106
IHC Intensity 1, n =189, 190 108 106
IHC Intensity 2, n=165, 146 94 85
IHC Intensity 3, n=64, 61 16 26
IHC Intensity Missing, n=73, 68 34 35
32.Secondary Outcome
Title Number of Participants With Response in Participants With Baseline Serum HER2 Extracellular Domain (ECD) Baseline Values Greater Than 15 Nanograms Per Milliliter (ng/mL) and 15 ng/mL or Lower
Hide Description The HER2 ECD is a glycoprotein that can be shed from the cell surface into the blood of normal individuals and can be elevated in different pathologic conditions. The serum HER2 ECD level generally reflects the tissue HER2 status. The HER2 ECD is quantified in serum with an enzyme-linked immunosorbent assay (ELISA). Non-Evaluable (NE): any participant who could not be classified as CR, PR, SD, or PD.
Time Frame Up to 46 months
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Hide Analysis Population Description
HER2-Positive Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 108 111
Measure Type: Number
Unit of Measure: participants
>15 ng/mL, CR/PR; n=53, 34 3 9
>15 ng/mL, SD; n=53, 34 11 13
>15 ng/mL, PD/NE; n=53, 34 39 12
=<15 ng/mL, CR/PR; n=51, 70 12 17
=<15 ng/mL, SD; n=51, 70 23 30
=<15 ng/mL, PD/NE; n=51, 70 16 23
33.Secondary Outcome
Title Number of HER2-Negative Participants at Baseline With and Without Seroconversion to a Status of HER2 Positive
Hide Description Participants who had a HER2-negative tumor status based on baseline tissue with baseline serum HER2 ECD values =<15 ng/mL but later had at least two consecutive serum HER2 ECD values >15 ng/mL experienced seroconversion.
Time Frame Up to 46 months
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Hide Analysis Population Description
HER2-Negative Population: all randomized participants regardless of whether or not study treatment had been received and who at baseline were evaluated by the central laboratory to have retrospectively documented non-amplification or missing amplification of HER2 by FISH (<2.0) and documented IHC scores of 0, 1+, 2+, or missing in tumor tissue.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 474 478
Measure Type: Number
Unit of Measure: participants
Seroconversion, No 323 140
Seroconversion, Yes 52 219
Missing 99 119
34.Secondary Outcome
Title Time to Seroconversion for Participants Who Were HER2 Negative at Baseline But Became HER2 Positive
Hide Description Time to seroconversion was defined as the time from the date of randomization until the first instance of serum HER2 (>15 ng/mL) on two consecutive occasions.
Time Frame Up to 46 months
Hide Outcome Measure Data
Hide Analysis Population Description
HER2-Negative Population. Only those participants who had a HER2-negative tumor status based on baseline tissue with baseline serum HER2 ECD values =<15 ng/mL but later had at least two consecutive serum HER2 ECD values >15 ng/mL were assessed.
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 52 219
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(NA to NA)
36.1
(24.0 to 48.9)
[1]
As >80% of the participants were censored, no median or confidence intervals could be established.
35.Secondary Outcome
Title Number of Participants With the Indicated Expression of Tumor by Epidermal Growth Factor Receptor (ErbB1/HER1/EGFR) at Baseline
Hide Description EGFR is a cell surface receptor tyrosine kinase expressed in certain types of tumors. Depending upon the staining intensity, EGFR was graded as follows: 0=absence of membrane staining above background in all tumor cells; EGFR-positive=staining is defined as any IHC staining of tumor cell membranes above background level, whether it is complete or incomplete circumferential staining (1+, 2+, 3+).
Time Frame Baseline
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Hide Analysis Population Description
ITT Population
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description:
Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
Overall Number of Participants Analyzed 644 642
Measure Type: Number
Unit of Measure: participants
EGFR, 3+ 3 1
EGFR, 0 to 2+ 573 579
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected during screening (within 4 weeks prior to the first dose), during study treatment (up to a maximum study duration of 46 months), and up to 30 days post-study.
Adverse Event Reporting Description SAEs and AEs were collected for the Safety Population, which included all randomized participants who had received at least 1 dose of study treatment, based on the actual treatment received if this differed from that to which the participant was randomized.
 
Arm/Group Title Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Hide Arm/Group Description Participants received 6 tablets of placebo, identical in appearance to lapatinib tablets, orally daily (approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 milligrams (mg) orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months. Participants received 6 tablets of lapatinib orally daily (250 mg lapatinib/tablet for a total of 1500 mg of lapatinib/day; approximately at the same time each day), either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received 1 tablet of letrozole 2.5 mg orally daily, preferably with the daily dose of lapatinib. The maximum treatment period was up to 46 months.
All-Cause Mortality
Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   94/624 (15.06%)   144/654 (22.02%) 
Blood and lymphatic system disorders     
Anaemia  1  2/624 (0.32%)  5/654 (0.76%) 
Febrile neutropenia  1  0/624 (0.00%)  2/654 (0.31%) 
Thrombocytopenia  1  0/624 (0.00%)  2/654 (0.31%) 
Leukocytosis  1  0/624 (0.00%)  1/654 (0.15%) 
Cardiac disorders     
Left ventricular dysfunction  1  1/624 (0.16%)  5/654 (0.76%) 
Atrial fibrillation  1  1/624 (0.16%)  2/654 (0.31%) 
Supraventricular tachycardia  1  2/624 (0.32%)  1/654 (0.15%) 
Cardiac failure  1  1/624 (0.16%)  1/654 (0.15%) 
Myocardial infarction  1  1/624 (0.16%)  1/654 (0.15%) 
Pericardial effusion  1  1/624 (0.16%)  1/654 (0.15%) 
Acute myocardial infarction  1  1/624 (0.16%)  0/654 (0.00%) 
Angina unstable  1  0/624 (0.00%)  1/654 (0.15%) 
Arrhythmia  1  1/624 (0.16%)  0/654 (0.00%) 
Cardio-respiratory arrest  1  1/624 (0.16%)  0/654 (0.00%) 
Left ventricular failure  1  1/624 (0.16%)  0/654 (0.00%) 
Palpitations  1  1/624 (0.16%)  0/654 (0.00%) 
Pericarditis  1  1/624 (0.16%)  0/654 (0.00%) 
Sinus tachycardia  1  0/624 (0.00%)  1/654 (0.15%) 
Ear and labyrinth disorders     
Deafness  1  1/624 (0.16%)  0/654 (0.00%) 
Endocrine disorders     
Inappropriate antidiuretic hormone secretion  1  0/624 (0.00%)  1/654 (0.15%) 
Eye disorders     
Visual disturbance  1  1/624 (0.16%)  0/654 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  2/624 (0.32%)  15/654 (2.29%) 
Vomiting  1  7/624 (1.12%)  10/654 (1.53%) 
Nausea  1  4/624 (0.64%)  5/654 (0.76%) 
Abdominal pain  1  2/624 (0.32%)  4/654 (0.61%) 
Ascites  1  0/624 (0.00%)  2/654 (0.31%) 
Colitis  1  1/624 (0.16%)  1/654 (0.15%) 
Constipation  1  2/624 (0.32%)  0/654 (0.00%) 
Gastrointestinal haemorrhage  1  0/624 (0.00%)  2/654 (0.31%) 
Haematemesis  1  0/624 (0.00%)  2/654 (0.31%) 
Intestinal obstruction  1  1/624 (0.16%)  1/654 (0.15%) 
Rectal haemorrhage  1  0/624 (0.00%)  2/654 (0.31%) 
Small intestinal obstruction  1  1/624 (0.16%)  1/654 (0.15%) 
Colonic obstruction  1  0/624 (0.00%)  1/654 (0.15%) 
Crohn’s disease  1  1/624 (0.16%)  0/654 (0.00%) 
Gastric ulcer  1  0/624 (0.00%)  1/654 (0.15%) 
Gastric ulcer perforation  1  1/624 (0.16%)  0/654 (0.00%) 
Haemorrhoids  1  1/624 (0.16%)  0/654 (0.00%) 
Ileus  1  1/624 (0.16%)  0/654 (0.00%) 
Intestinal ischaemia  1  0/624 (0.00%)  1/654 (0.15%) 
Melaena  1  0/624 (0.00%)  1/654 (0.15%) 
Pancreatitis  1  0/624 (0.00%)  1/654 (0.15%) 
Pancreatitis haemorrhagic  1  1/624 (0.16%)  0/654 (0.00%) 
General disorders     
Pyrexia  1  4/624 (0.64%)  4/654 (0.61%) 
Chest pain  1  3/624 (0.48%)  3/654 (0.46%) 
Asthenia  1  1/624 (0.16%)  3/654 (0.46%) 
General physical health deterioration  1  1/624 (0.16%)  1/654 (0.15%) 
Catheter related complication  1  1/624 (0.16%)  0/654 (0.00%) 
Fatigue  1  0/624 (0.00%)  1/654 (0.15%) 
Gait disturbance  1  1/624 (0.16%)  0/654 (0.00%) 
Hernia obstructive  1  0/624 (0.00%)  1/654 (0.15%) 
Malaise  1  1/624 (0.16%)  0/654 (0.00%) 
Multi-organ failure  1  0/624 (0.00%)  1/654 (0.15%) 
Non-cardiac chest pain  1  0/624 (0.00%)  1/654 (0.15%) 
Oedema peripheral  1  1/624 (0.16%)  0/654 (0.00%) 
Hepatobiliary disorders     
Hepatotoxicity  1  2/624 (0.32%)  1/654 (0.15%) 
Hepatic function abnormal  1  0/624 (0.00%)  2/654 (0.31%) 
Cholecystitis  1  0/624 (0.00%)  1/654 (0.15%) 
Cholecystitis acute  1  0/624 (0.00%)  1/654 (0.15%) 
Gallbladder disorder  1  0/624 (0.00%)  1/654 (0.15%) 
Gallbladder pain  1  0/624 (0.00%)  1/654 (0.15%) 
Hepatorenal failure  1  0/624 (0.00%)  1/654 (0.15%) 
Jaundice  1  0/624 (0.00%)  1/654 (0.15%) 
Infections and infestations     
Urinary tract infection  1  1/624 (0.16%)  6/654 (0.92%) 
Erysipelas  1  2/624 (0.32%)  4/654 (0.61%) 
Cellulitis  1  0/624 (0.00%)  5/654 (0.76%) 
Pneumonia  1  3/624 (0.48%)  2/654 (0.31%) 
Lung infection  1  1/624 (0.16%)  2/654 (0.31%) 
Pyelonephritis  1  2/624 (0.32%)  1/654 (0.15%) 
Breast cellulitis  1  1/624 (0.16%)  1/654 (0.15%) 
Lower respiratory tract infection  1  0/624 (0.00%)  2/654 (0.31%) 
Paronychia  1  0/624 (0.00%)  2/654 (0.31%) 
Sepsis  1  1/624 (0.16%)  1/654 (0.15%) 
Septic shock  1  0/624 (0.00%)  2/654 (0.31%) 
Breast abscess  1  0/624 (0.00%)  1/654 (0.15%) 
Bronchopneumonia  1  1/624 (0.16%)  0/654 (0.00%) 
Catheter site infection  1  1/624 (0.16%)  0/654 (0.00%) 
Diverticulitis  1  0/624 (0.00%)  1/654 (0.15%) 
Furuncle  1  0/624 (0.00%)  1/654 (0.15%) 
Gastroenteritis  1  1/624 (0.16%)  0/654 (0.00%) 
Herpes zoster  1  0/624 (0.00%)  1/654 (0.15%) 
Incision site cellulitis  1  0/624 (0.00%)  1/654 (0.15%) 
Infected skin ulcer  1  1/624 (0.16%)  0/654 (0.00%) 
Infection  1  0/624 (0.00%)  1/654 (0.15%) 
Lobar pneumonia  1  0/624 (0.00%)  1/654 (0.15%) 
Localised infection  1  1/624 (0.16%)  0/654 (0.00%) 
Oral infection  1  0/624 (0.00%)  1/654 (0.15%) 
Peritonitis bacterial  1  0/624 (0.00%)  1/654 (0.15%) 
Post procedural infection  1  0/624 (0.00%)  1/654 (0.15%) 
Respiratory tract infection  1  1/624 (0.16%)  0/654 (0.00%) 
Tooth abscess  1  1/624 (0.16%)  0/654 (0.00%) 
Urosepsis  1  0/624 (0.00%)  1/654 (0.15%) 
Vulval abscess  1  0/624 (0.00%)  1/654 (0.15%) 
Wound infection  1  0/624 (0.00%)  1/654 (0.15%) 
Injury, poisoning and procedural complications     
Femur fracture  1  1/624 (0.16%)  3/654 (0.46%) 
Hip fracture  1  2/624 (0.32%)  0/654 (0.00%) 
Ankle fracture  1  0/624 (0.00%)  1/654 (0.15%) 
Cervical vertebral fracture  1  1/624 (0.16%)  0/654 (0.00%) 
Compression fracture  1  1/624 (0.16%)  0/654 (0.00%) 
Device breakage  1  1/624 (0.16%)  0/654 (0.00%) 
Eye injury  1  1/624 (0.16%)  0/654 (0.00%) 
Fall  1  0/624 (0.00%)  1/654 (0.15%) 
Femoral neck fracture  1  0/624 (0.00%)  1/654 (0.15%) 
Humerus fracture  1  0/624 (0.00%)  1/654 (0.15%) 
Intraocular lens dislocation  1  0/624 (0.00%)  1/654 (0.15%) 
Overdose  1  0/624 (0.00%)  1/654 (0.15%) 
Pelvic fracture  1  0/624 (0.00%)  1/654 (0.15%) 
Post procedural complication  1  1/624 (0.16%)  0/654 (0.00%) 
Road traffic accident  1  1/624 (0.16%)  0/654 (0.00%) 
Spinal compression fracture  1  0/624 (0.00%)  1/654 (0.15%) 
Synovial rupture  1  1/624 (0.16%)  0/654 (0.00%) 
Therapeutic agent toxicity  1  0/624 (0.00%)  1/654 (0.15%) 
Tibia fracture  1  0/624 (0.00%)  1/654 (0.15%) 
Upper limb fracture  1  1/624 (0.16%)  0/654 (0.00%) 
Wrist fracture  1  0/624 (0.00%)  1/654 (0.15%) 
Investigations     
Ejection fraction decreased  1  8/624 (1.28%)  17/654 (2.60%) 
Blood alkaline phosphatase increased  1  1/624 (0.16%)  1/654 (0.15%) 
Alanine aminotransferase increased  1  0/624 (0.00%)  1/654 (0.15%) 
Aspartate aminotransferase increased  1  1/624 (0.16%)  0/654 (0.00%) 
Blood urea increased  1  0/624 (0.00%)  1/654 (0.15%) 
Gamma-glutamyltransferase increased  1  0/624 (0.00%)  1/654 (0.15%) 
Hepatic enzyme increased  1  0/624 (0.00%)  1/654 (0.15%) 
Metabolism and nutrition disorders     
Dehydration  1  2/624 (0.32%)  7/654 (1.07%) 
Anorexia  1  2/624 (0.32%)  1/654 (0.15%) 
Hypercalcaemia  1  2/624 (0.32%)  0/654 (0.00%) 
Hyperglycaemia  1  1/624 (0.16%)  1/654 (0.15%) 
Hyperuricaemia  1  0/624 (0.00%)  2/654 (0.31%) 
Hypokalaemia  1  2/624 (0.32%)  0/654 (0.00%) 
Diabetes mellitus  1  1/624 (0.16%)  0/654 (0.00%) 
Electrolyte imbalance  1  0/624 (0.00%)  1/654 (0.15%) 
Hypercreatininaemia  1  1/624 (0.16%)  0/654 (0.00%) 
Hypocalcaemia  1  1/624 (0.16%)  0/654 (0.00%) 
Hypoglycaemia  1  1/624 (0.16%)  0/654 (0.00%) 
Hyponatraemia  1  0/624 (0.00%)  1/654 (0.15%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  5/624 (0.80%)  2/654 (0.31%) 
Arthralgia  1  0/624 (0.00%)  2/654 (0.31%) 
Bone pain  1  1/624 (0.16%)  1/654 (0.15%) 
Neck pain  1  0/624 (0.00%)  2/654 (0.31%) 
Pathological fracture  1  1/624 (0.16%)  1/654 (0.15%) 
Flank pain  1  1/624 (0.16%)  0/654 (0.00%) 
Hypercreatinaemia  1  0/624 (0.00%)  1/654 (0.15%) 
Musculoskeletal chest pain  1  1/624 (0.16%)  0/654 (0.00%) 
Musculoskeletal pain  1  0/624 (0.00%)  1/654 (0.15%) 
Osteoarthritis  1  0/624 (0.00%)  1/654 (0.15%) 
Pain in extremity  1  0/624 (0.00%)  1/654 (0.15%) 
Rhabdomyolysis  1  0/624 (0.00%)  1/654 (0.15%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia  1  0/624 (0.00%)  1/654 (0.15%) 
Breast cancer metastatic  1  0/624 (0.00%)  1/654 (0.15%) 
Carcinoid tumour  1  0/624 (0.00%)  1/654 (0.15%) 
Lymphoma  1  1/624 (0.16%)  0/654 (0.00%) 
Renal cell carcinoma  1  0/624 (0.00%)  1/654 (0.15%) 
Transitional cell carcinoma  1  0/624 (0.00%)  1/654 (0.15%) 
Nervous system disorders     
Syncope  1  1/624 (0.16%)  2/654 (0.31%) 
Cerebrovascular accident  1  1/624 (0.16%)  1/654 (0.15%) 
Headache  1  2/624 (0.32%)  0/654 (0.00%) 
Hemiparesis  1  2/624 (0.32%)  0/654 (0.00%) 
Ataxia  1  1/624 (0.16%)  0/654 (0.00%) 
Cerebrovascular disorder  1  0/624 (0.00%)  1/654 (0.15%) 
Cognitive disorder  1  1/624 (0.16%)  0/654 (0.00%) 
Dementia Alzheimer’s type  1  1/624 (0.16%)  0/654 (0.00%) 
Depressed level of consciousness  1  0/624 (0.00%)  1/654 (0.15%) 
Dizziness  1  1/624 (0.16%)  0/654 (0.00%) 
Encephalopathy  1  1/624 (0.16%)  0/654 (0.00%) 
Facial palsy  1  0/624 (0.00%)  1/654 (0.15%) 
Facial paresis  1  1/624 (0.16%)  0/654 (0.00%) 
Ischaemic stroke  1  1/624 (0.16%)  0/654 (0.00%) 
Paraparesis  1  1/624 (0.16%)  0/654 (0.00%) 
Colon cancer  1  0/624 (0.00%)  1/654 (0.15%) 
Psychiatric disorders     
Confusional state  1  1/624 (0.16%)  1/654 (0.15%) 
Anxiety  1  0/624 (0.00%)  1/654 (0.15%) 
Hallucination, visual  1  1/624 (0.16%)  0/654 (0.00%) 
Renal and urinary disorders     
Renal failure  1  1/624 (0.16%)  2/654 (0.31%) 
Hydronephrosis  1  1/624 (0.16%)  1/654 (0.15%) 
Nephrolithiasis  1  0/624 (0.00%)  1/654 (0.15%) 
Pelvi-ureteric obstruction  1  1/624 (0.16%)  0/654 (0.00%) 
Renal failure acute  1  0/624 (0.00%)  1/654 (0.15%) 
Renal impairment  1  1/624 (0.16%)  0/654 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst  1  0/624 (0.00%)  1/654 (0.15%) 
Ovarian enlargement  1  0/624 (0.00%)  1/654 (0.15%) 
Pelvic pain  1  1/624 (0.16%)  0/654 (0.00%) 
Uterine haemorrhage  1  0/624 (0.00%)  1/654 (0.15%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  4/624 (0.64%)  5/654 (0.76%) 
Pulmonary embolism  1  3/624 (0.48%)  3/654 (0.46%) 
Pleural effusion  1  1/624 (0.16%)  2/654 (0.31%) 
Haemoptysis  1  0/624 (0.00%)  2/654 (0.31%) 
Hypoxia  1  0/624 (0.00%)  2/654 (0.31%) 
Pneumothorax  1  1/624 (0.16%)  1/654 (0.15%) 
Acute pulmonary oedema  1  0/624 (0.00%)  1/654 (0.15%) 
Epistaxis  1  1/624 (0.16%)  0/654 (0.00%) 
Haemothorax  1  0/624 (0.00%)  1/654 (0.15%) 
Idiopathic pulmonary fibrosis  1  0/624 (0.00%)  1/654 (0.15%) 
Interstitial lung disease  1  0/624 (0.00%)  1/654 (0.15%) 
Pleuritic pain  1  0/624 (0.00%)  1/654 (0.15%) 
Pulmonary hypertension  1  0/624 (0.00%)  1/654 (0.15%) 
Tachypnoea  1  0/624 (0.00%)  1/654 (0.15%) 
Skin and subcutaneous tissue disorders     
Rash  1  0/624 (0.00%)  2/654 (0.31%) 
Dermatomyositis  1  0/624 (0.00%)  1/654 (0.15%) 
Excessive granulation tissue  1  0/624 (0.00%)  1/654 (0.15%) 
Pruritus  1  0/624 (0.00%)  1/654 (0.15%) 
Toxic skin eruption  1  0/624 (0.00%)  1/654 (0.15%) 
Vascular disorders     
Deep vein thrombosis  1  2/624 (0.32%)  2/654 (0.31%) 
Haematoma  1  0/624 (0.00%)  1/654 (0.15%) 
Hypertension  1  1/624 (0.16%)  0/654 (0.00%) 
Hypotension  1  1/624 (0.16%)  0/654 (0.00%) 
Lymphoedema  1  1/624 (0.16%)  0/654 (0.00%) 
Superior vena caval occlusion  1  0/624 (0.00%)  1/654 (0.15%) 
Thrombophlebitis  1  0/624 (0.00%)  1/654 (0.15%) 
Thrombosis  1  1/624 (0.16%)  0/654 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Letrozole 2.5 mg Plus Placebo Letrozole 2.5 mg Plus Lapatinib 1500 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   500/624 (80.13%)   605/654 (92.51%) 
Blood and lymphatic system disorders     
Anaemia  1  27/624 (4.33%)  49/654 (7.49%) 
Gastrointestinal disorders     
Diarrhoea  1  122/624 (19.55%)  416/654 (63.61%) 
Nausea  1  126/624 (20.19%)  199/654 (30.43%) 
Vomiting  1  64/624 (10.26%)  104/654 (15.90%) 
Constipation  1  65/624 (10.42%)  60/654 (9.17%) 
Dyspepsia  1  36/624 (5.77%)  61/654 (9.33%) 
Abdominal pain  1  27/624 (4.33%)  49/654 (7.49%) 
Abdominal pain upper  1  20/624 (3.21%)  36/654 (5.50%) 
Stomatitis  1  6/624 (0.96%)  32/654 (4.89%) 
Arthralgia  1  145/624 (23.24%)  127/654 (19.42%) 
General disorders     
Fatigue  1  108/624 (17.31%)  133/654 (20.34%) 
Asthenia  1  68/624 (10.90%)  78/654 (11.93%) 
Oedema peripheral  1  51/624 (8.17%)  43/654 (6.57%) 
Pyrexia  1  35/624 (5.61%)  44/654 (6.73%) 
Mucosal inflammation  1  13/624 (2.08%)  41/654 (6.27%) 
Infections and infestations     
Nasopharyngitis  1  45/624 (7.21%)  55/654 (8.41%) 
Urinary tract infection  1  48/624 (7.69%)  35/654 (5.35%) 
Upper respiratory tract infection  1  31/624 (4.97%)  31/654 (4.74%) 
Paronychia  1  1/624 (0.16%)  37/654 (5.66%) 
Investigations     
Alanine aminotransferase increased  1  28/624 (4.49%)  56/654 (8.56%) 
Aspartate aminotransferase increased  1  22/624 (3.53%)  52/654 (7.95%) 
Weight decreased  1  12/624 (1.92%)  36/654 (5.50%) 
Blood alkaline phosphatase increased  1  15/624 (2.40%)  30/654 (4.59%) 
Metabolism and nutrition disorders     
Anorexia  1  53/624 (8.49%)  71/654 (10.86%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  94/624 (15.06%)  103/654 (15.75%) 
Pain in extremity  1  71/624 (11.38%)  66/654 (10.09%) 
Musculoskeletal pain  1  56/624 (8.97%)  52/654 (7.95%) 
Bone pain  1  54/624 (8.65%)  35/654 (5.35%) 
Myalgia  1  43/624 (6.89%)  34/654 (5.20%) 
Musculoskeletal chest pain  1  41/624 (6.57%)  32/654 (4.89%) 
Muscle spasms  1  24/624 (3.85%)  39/654 (5.96%) 
Nervous system disorders     
Headache  1  81/624 (12.98%)  91/654 (13.91%) 
Dizziness  1  50/624 (8.01%)  48/654 (7.34%) 
Psychiatric disorders     
Insomnia  1  55/624 (8.81%)  42/654 (6.42%) 
Anxiety  1  28/624 (4.49%)  32/654 (4.89%) 
Depression  1  25/624 (4.01%)  32/654 (4.89%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  90/624 (14.42%)  80/654 (12.23%) 
Dyspnoea  1  69/624 (11.06%)  60/654 (9.17%) 
Epistaxis  1  10/624 (1.60%)  70/654 (10.70%) 
Pharyngolaryngeal pain  1  22/624 (3.53%)  31/654 (4.74%) 
Skin and subcutaneous tissue disorders     
Rash  1  80/624 (12.82%)  290/654 (44.34%) 
Pruritus  1  55/624 (8.81%)  80/654 (12.23%) 
Alopecia  1  45/624 (7.21%)  85/654 (13.00%) 
Dry skin  1  27/624 (4.33%)  87/654 (13.30%) 
Nail disorder  1  6/624 (0.96%)  73/654 (11.16%) 
Dermatitis acneiform  1  1/624 (0.16%)  35/654 (5.35%) 
Vascular disorders     
Hot flush  1  92/624 (14.74%)  69/654 (10.55%) 
Hypertension  1  26/624 (4.17%)  34/654 (5.20%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00073528     History of Changes
Obsolete Identifiers: NCT00084968
Other Study ID Numbers: EGF30008
First Submitted: November 24, 2003
First Posted: November 26, 2003
Results First Submitted: April 19, 2012
Results First Posted: May 17, 2012
Last Update Posted: October 4, 2018