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A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01160211
Recruitment Status : Completed
First Posted : July 12, 2010
Results First Posted : July 15, 2019
Last Update Posted : June 30, 2022
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms, Breast
Interventions Drug: lapatinib
Drug: trastuzumab
Drug: Aromatase inhibitor
Enrollment 369
Recruitment Details A total of 355 subjects were enrolled in the study at the time of the cut-off date for analysis. After the cutoff date (11 Mar 2016), 14 additional subjects were enrolled; however no data from these subjects are reported in this report. Analysis was done on the Intent-to-Treat (ITT) population.
Pre-assignment Details The ITT comprised all randomized subjects regardless of whether or not treatment was administered. This population was based on the treatment to which the subject was randomized.
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors) Lapatinib (1500mg) plus AI (Aromatase Inhibitors) Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Period Title: Overall Study
Started 120 118 117
Ongoing 90 75 79
Completed 21 31 30
Not Completed 99 87 87
Reason Not Completed
ongoing             90             75             79
Withdrawal by Subject             3             5             3
Physician Decision             2             0             0
Lost to Follow-up             4             7             5
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI Total
Hide Arm/Group Description lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors) Lapatinib (1500mg) plus AI (Aromatase Inhibitors) Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors) Total of all reporting groups
Overall Number of Baseline Participants 120 118 117 355
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) population comprised all randomized subjects regardless of whether or not treatment was administered. ITT was based on the treatment to which the subject was randomized and was the primary population for the analysis of efficacy data. Any subject who received a treatment randomization # was considered to have been randomized.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 120 participants 118 participants 117 participants 355 participants
56.8  (10.88) 57.2  (9.94) 55.2  (9.78) 56.4  (10.23)
[1]
Measure Analysis Population Description: ITT population
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 118 participants 117 participants 355 participants
Female
120
 100.0%
118
 100.0%
117
 100.0%
355
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: ITT
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 118 participants 117 participants 355 participants
Hispanic or Latino
23
  19.2%
23
  19.5%
20
  17.1%
66
  18.6%
Not Hispanic or Latino
97
  80.8%
95
  80.5%
97
  82.9%
289
  81.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title PFS of Lapatinib+Trastuzumab+AI Combination vs. Trastuzumab+AI Combination
Hide Description Progression free survival (PFS) of lapatinib/trastuzumab/aromatase inhibitor (AI) combination vs. trastuzumab/AI combination. PFS is defined as the time from randomization to the earliest date of disease progression (with radiological evidence) or death from any cause, or to the date of censor.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Lapatinib+Trastuzumab+Al Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 117
Measure Type: Count of Participants
Unit of Measure: Participants
Disease progression or died (event)
62
  51.7%
75
  64.1%
Censored, follow-up for disease progression ended
7
   5.8%
3
   2.6%
Censored, f/p for disease progression ongoing
51
  42.5%
39
  33.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments Null hypothesis H0: λ ≥ 1 or to reject it in favor of the alternative hypothesis HA: λ <1, where λ is the hazard ratio (HR) between Treatment Group A and Treatment Group B for progression-free survival.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0063
Comments Pike estimate of the treatment hazard ratio, <1 indicates a lower risk compared with trastuzumab + AI.
Method Log Rank
Comments using a two-sided stratified log-rank test (based on stratification factors)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.45 to 0.88
Estimation Comments [Not Specified]
2.Primary Outcome
Title Median Kaplan Meier Estimates for PFS of Lapatinib+Trastuzumab+AI Combination vs. Trastuzumab+AI Combination
Hide Description Progression free survival (PFS) of lapatinib/trastuzumab/aromatase inhibitor (AI) combination vs. trastuzumab/AI combination. PFS is defined as the time from randomization to the earliest date of disease progression (with radiological evidence) or death from any cause, or to the date of censor.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Lapatinib+Trastuzumab+Al Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 117
Median (95% Confidence Interval)
Unit of Measure: Months
11.0
(8.3 to 13.8)
5.6
(5.4 to 8.3)
3.Secondary Outcome
Title PFS of Trastuzumab/AI vs. Lapatinib/AI and Trastuzumab/Lapatinib/AI vs. Lapatinib/AI
Hide Description PFS in the lapatinib arm vs. the trastuzumab arm and in the lapatinib+trastuzumab arm vs. the lapatinib arm.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Lapatinib (1500mg) plus AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 118 117
Measure Type: Count of Participants
Unit of Measure: Participants
Disease progression or died (event)
62
  51.7%
75
  63.6%
75
  64.1%
Censored, follow-up ended
7
   5.8%
6
   5.1%
3
   2.6%
Censored, follow-up ongoing
51
  42.5%
37
  31.4%
39
  33.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3159
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.62 to 1.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Lapatinib+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0824
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.53 to 1.04
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Overall Survival (OS) Events of Lapatinib+Trastuzumab+AI vs. Trastuzumab+AI and Lapatinib+AI vs. Trastuzumab+AI
Hide Description OS was defined as the interval of time (in weeks) between the date of randomization and the date of death due to any cause. For subjects who did not die during the study, death was censored at the date of last contact.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Lapatinib (1500mg) plus AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 118 117
Measure Type: Count of Participants
Unit of Measure: Participants
Death
21
  17.5%
31
  26.3%
30
  25.6%
Censored, follow-up ended
9
   7.5%
12
  10.2%
8
   6.8%
Censored, follow-up ongoing
90
  75.0%
75
  63.6%
79
  67.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.070
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.35 to 1.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.718
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.55 to 1.51
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Overall Response Rate (ORR; Complete or Partial Response) in Lapatinib+Trastuzumab+AI vs. Trastuzumab+AI and Lapatinib+AI vs. Trastuzumab+AI
Hide Description The best overall response was the best response recorded from the start of the treatment until disease progression/recurrence & was determined programmatically using investigators assessment of responses of target lesion, non-target lesion and new lesions based on RECIST v1.1. CR=disappearance of all target lesion & non-target lesions, if applicable, and no new lesion; PR = ≥30% decrease in the sum of the longest diameter of target lesions & non-target lesion was neither non-CR nor progressive disease (Non-PD) or not evaluable (NE); stable disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (SD should maintain for at least 56 days); PD = ≥20% increase from nadir (smallest sum diameters recorded since treatment start) of the target lesions and/or any status for non-target lesions or appearance of new lesion; NE = cannot be classified by the above definitions. Overall Response (OR) = CR + PR.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Lapatinib (1500mg) plus AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 118 117
Measure Type: Count of Participants
Unit of Measure: Participants
38
  31.7%
22
  18.6%
16
  13.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method exact test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.830
Confidence Interval (2-Sided) 95%
1.426 to 5.888
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2829
Comments [Not Specified]
Method Exact Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.492
Confidence Interval (2-Sided) 95%
0.685 to 3.296
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Clinical Benefit Rate (CBR; Complete Response, Partial Response, or Stable Disease for at Least 6 Months) in Lapatinib+Trastuzumab+AI vs. Trastuzumab+AI and Lapatinib+AI vs. Trastuzumab+AI
Hide Description Clinical Benefit Rate (CBR) was defined as the percentage of patients with evidence of complete response (CR) or partial response (PR) at any time or maintaining SD for at least 24 weeks while on study, according to the investigator assessment of response per RECIST 1.1 criteria.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Lapatinib (1500mg) plus AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 118 117
Measure Type: Count of Participants
Unit of Measure: Participants
48
  40.0%
40
  33.9%
35
  29.9%
7.Secondary Outcome
Title Duration of Response in Lapatinib+Trastuzumab+AI vs. Trastuzumab+AI and Lapatinib+AI vs. Trastuzumab+AI
Hide Description Kaplan-Meier estimates for duration of response in lapatinib+trastuzumab+AI vs. trastuzumab+AI and lapatinib+AI vs. trastuzumab+AI. Duration of response is defined as the time from first documented Complete Response or Partial Response until the first documented sign of Progressive Disease or Death, or to the date of censor.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Lapatinib (1500mg) plus AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 118 117
Median (95% Confidence Interval)
Unit of Measure: Months
14.0
(5.7 to 33.2)
11.1 [1] 
(5.5 to NA)
8.4 [1] 
(3.0 to NA)
[1]
not estimable
8.Secondary Outcome
Title Changes in the Quality of Life (QoL) Status Relative to Baseline FACT-B Overall and Subscale Scores at Last On-treatment Assessment
Hide Description Quality of life was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. It is a 37-item (27 general questions and 10 breast cancer specific questions) self-reporting instrument consisting of 5 dimensions: physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and a breast cancer subscale (BCS). The followings are the score ranges for each self-reporting subscale: • PWB : 0-28 • SWB : 0-28 • EWB : 0-24 • FWB : 0-28 • BCS : 0-40 FACT-B Total Outcome Index (TOI) = PWB + FWB + BCS (range:0 - 96) FACT-B Total Score = PWB + SWB + EWB + FWB + BCS (range:0-148) FACT-G Total Score = PWB + SWB + EWB + FWB (range:0-108) In the scoring system, negative stated items are reversed by subtracting the response from "4" and after reversing proper items, all subscale items are summed to a total, which is the subscale score. For all the FACIT scales and symptom indices, the higher the score the better cut off
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Lapatinib (1500mg) plus AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 118 117
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
FACT-B total score Number Analyzed 105 participants 104 participants 101 participants
-3.0  (1.47) -4.4  (1.48) -1.3  (1.50)
FACT-G total score Number Analyzed 105 participants 105 participants 101 participants
-3.4  (1.22) -4.1  (1.22) -1.6  (1.24)
FACT-B trial outcome Index (TOI) Number Analyzed 105 participants 105 participants 101 participants
-2.2  (1.05) -3.2  (1.05) -0.3  (1.07)
Physical well-being (PWB) Number Analyzed 106 participants 107 participants 101 participants
-1.6  (0.48) -1.5  (0.48) -0.5  (0.49)
Social family wellbeing (SWB) Number Analyzed 106 participants 106 participants 101 participants
-0.7  (0.49) -1.0  (0.49) -0.5  (0.50)
Emotional wellbeing (EWB) Number Analyzed 106 participants 107 participants 101 participants
-0.1  (0.40) -0.1  (0.39) -0.5  (0.40)
Functional wellbeing (FWB) Number Analyzed 106 participants 107 participants 101 participants
-1.0  (0.45) -1.4  (0.45) -0.1  (0.47)
Breast cancer subscale (BCS) Number Analyzed 106 participants 107 participants 101 participants
0.4  (0.48) -0.3  (0.47) 0.3  (0.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments FACT-B total score
Statistical Test of Hypothesis P-Value 0.4061
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -1.75
Confidence Interval (2-Sided) 95%
-5.88 to 2.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.102
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments FACT-B total score
Statistical Test of Hypothesis P-Value 0.1364
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least saquares defference
Estimated Value -3.15
Confidence Interval (2-Sided) 95%
-7.29 to 1.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.107
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments FACT-G total score
Statistical Test of Hypothesis P-Value 0.3032
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square difference
Estimated Value -1.79
Confidence Interval (2-Sided) 95%
-5.22 to 1.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.739
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments FACT-G total score
Statistical Test of Hypothesis P-Value 0.1509
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -2.50
Confidence Interval (2-Sided) 95%
-5.93 to 0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.739
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments FACT-B trial outcome index (TOI)
Statistical Test of Hypothesis P-Value 0.2088
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -1.89
Confidence Interval (2-Sided) 95%
-4.84 to 1.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.498
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments FACT-B trial outcome index (TOI)
Statistical Test of Hypothesis P-Value 0.0506
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -2.94
Confidence Interval (2-Sided) 95%
-5.89 to 0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.499
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Physical well-being (PWB)
Statistical Test of Hypothesis P-Value 0.1369
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-2.39 to 0.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.690
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Physical well-being (PWB)
Statistical Test of Hypothesis P-Value 0.1666
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -0.96
Confidence Interval (2-Sided) 95%
-2.31 to 0.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.689
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Social family wellbeing (SWB)
Statistical Test of Hypothesis P-Value 0.7672
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least sqaures difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-1.58 to 1.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.699
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Social family wellbeing (SWB)
Statistical Test of Hypothesis P-Value 0.4471
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-1.91 to 0.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.699
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Emotional wellbeing (EWB)
Statistical Test of Hypothesis P-Value 0.4284
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
-0.66 to 1.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.565
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Emotional wellbeing (EWB)
Statistical Test of Hypothesis P-Value 0.4350
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
-0.67 to 1.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.564
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Functional wellbeing (FWB)
Statistical Test of Hypothesis P-Value 0.1598
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-2.20 to 0.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.651
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Functional wellbeing (FWB)
Statistical Test of Hypothesis P-Value 0.0371
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value -1.36
Confidence Interval (2-Sided) 95%
-2.64 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.649
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Lapatinib+Trastuzumab+Al, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Breast cancer subscale (BCS)
Statistical Test of Hypothesis P-Value 0.9552
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-1.30 to 1.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.681
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Lapatinib+AI, Trastuzumab+AI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Breast cancer subscale (BCS)
Statistical Test of Hypothesis P-Value 0.3100
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Leasst squares difference
Estimated Value -0.69
Confidence Interval (2-Sided) 95%
-2.03 to 0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.680
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to Response in Lapatinib+Trastuzumab+AI vs. Trastuzumab+AI and Lapatinib+AI vs. Trastuzumab+AI
Hide Description Time to response in lapatinib+trastuzumab+AI vs. trastuzumab+AI and lapatinib+AI vs. trastuzumab+AI. Time to response is defined as time from randomization to first documented Complete Response or Partial Response.
Time Frame approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description:
lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors)
Lapatinib (1500mg) plus AI (Aromatase Inhibitors)
Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
Overall Number of Participants Analyzed 120 118 117
Median (Full Range)
Unit of Measure: Days
85.0
(72 to 598)
86.0
(65 to 423)
89.0
(68 to 335)
Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for the interim analysis. All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit of the interim analysis, up to approximately 5 years
Adverse Event Reporting Description The assessment was done in the safety population which included 353 subjects. Two subjects randomized to trastuzumab did not receive any study treatment and were therefore excluded from the safety population.
 
Arm/Group Title Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Hide Arm/Group Description lapatinib (1000mg) plus trastuzumab (6mg/kg) plus an AI (Aromatase Inhibitors) Lapatinib (1500mg) plus AI (Aromatase Inhibitors) Trastuzumab (6 mg/kg) +AI (Aromatase Inhibitors)
All-Cause Mortality
Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/118 (17.80%)   31/119 (26.05%)   30/116 (25.86%) 
Hide Serious Adverse Events
Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/118 (13.56%)   20/119 (16.81%)   12/116 (10.34%) 
Blood and lymphatic system disorders       
Anaemia † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Febrile neutropenia † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Cardiac disorders       
Acute myocardial infarction † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Cardiac disorder † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Cardiac failure † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Cardio-respiratory arrest † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Cardiogenic shock † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Gastrointestinal disorders       
Anal fissure † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Ascites † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Diarrhoea † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Gastritis † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
General disorders       
Asthenia † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Pain † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Sudden death † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Hepatobiliary disorders       
Hepatic failure † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Immune system disorders       
Drug hypersensitivity † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Iodine allergy † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Infections and infestations       
Cellulitis † 1  2/118 (1.69%)  1/119 (0.84%)  2/116 (1.72%) 
Herpes zoster † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Lower respiratory tract infection † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Urinary tract infection † 1  1/118 (0.85%)  0/119 (0.00%)  1/116 (0.86%) 
Urosepsis † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Injury, poisoning and procedural complications       
Femur fracture † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Hip fracture † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Ligament sprain † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Muscle strain † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Post procedural inflammation † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Spinal compression fracture † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Investigations       
Alanine aminotransferase increased † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Ejection fraction decreased † 1  3/118 (2.54%)  1/119 (0.84%)  2/116 (1.72%) 
Metabolism and nutrition disorders       
Dehydration † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Hypercalcaemia † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Hypocalcaemia † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Hypokalaemia † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Musculoskeletal and connective tissue disorders       
Pathological fracture † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Rheumatoid arthritis † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastases to lung † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Ovarian epithelial cancer † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Nervous system disorders       
Headache † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Intracranial aneurysm † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Speech disorder † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Psychiatric disorders       
Confusional state † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Renal and urinary disorders       
Acute kidney injury † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Pyelocaliectasis † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Renal failure † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Haemoptysis † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
Hydrothorax † 1  1/118 (0.85%)  0/119 (0.00%)  0/116 (0.00%) 
Pleural effusion † 1  0/118 (0.00%)  1/119 (0.84%)  1/116 (0.86%) 
Pneumothorax † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Pulmonary embolism † 1  0/118 (0.00%)  1/119 (0.84%)  0/116 (0.00%) 
Respiratory failure † 1  0/118 (0.00%)  0/119 (0.00%)  1/116 (0.86%) 
1
Term from vocabulary, MedDRA (20.1)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lapatinib+Trastuzumab+Al Lapatinib+AI Trastuzumab+AI
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   108/118 (91.53%)   104/119 (87.39%)   80/116 (68.97%) 
Blood and lymphatic system disorders       
Anaemia † 1  6/118 (5.08%)  7/119 (5.88%)  8/116 (6.90%) 
Gastrointestinal disorders       
Abdominal pain upper † 1  9/118 (7.63%)  6/119 (5.04%)  8/116 (6.90%) 
Diarrhoea † 1  81/118 (68.64%)  61/119 (51.26%)  10/116 (8.62%) 
Dyspepsia † 1  8/118 (6.78%)  4/119 (3.36%)  0/116 (0.00%) 
Nausea † 1  26/118 (22.03%)  26/119 (21.85%)  11/116 (9.48%) 
Stomatitis † 1  20/118 (16.95%)  15/119 (12.61%)  4/116 (3.45%) 
Vomiting † 1  12/118 (10.17%)  17/119 (14.29%)  1/116 (0.86%) 
General disorders       
Asthenia † 1  10/118 (8.47%)  7/119 (5.88%)  6/116 (5.17%) 
Fatigue † 1  14/118 (11.86%)  17/119 (14.29%)  12/116 (10.34%) 
Oedema peripheral † 1  6/118 (5.08%)  4/119 (3.36%)  3/116 (2.59%) 
Pyrexia † 1  6/118 (5.08%)  5/119 (4.20%)  6/116 (5.17%) 
Infections and infestations       
Nasopharyngitis † 1  8/118 (6.78%)  5/119 (4.20%)  10/116 (8.62%) 
Paronychia † 1  35/118 (29.66%)  18/119 (15.13%)  0/116 (0.00%) 
Upper respiratory tract infection † 1  10/118 (8.47%)  8/119 (6.72%)  6/116 (5.17%) 
Investigations       
Alanine aminotransferase increased † 1  8/118 (6.78%)  17/119 (14.29%)  7/116 (6.03%) 
Aspartate aminotransferase increased † 1  7/118 (5.93%)  20/119 (16.81%)  10/116 (8.62%) 
Blood alkaline phosphatase increased † 1  4/118 (3.39%)  5/119 (4.20%)  9/116 (7.76%) 
Blood bilirubin increased † 1  2/118 (1.69%)  7/119 (5.88%)  1/116 (0.86%) 
Blood uric acid increased † 1  5/118 (4.24%)  6/119 (5.04%)  1/116 (0.86%) 
Weight decreased † 1  11/118 (9.32%)  9/119 (7.56%)  3/116 (2.59%) 
Metabolism and nutrition disorders       
Decreased appetite † 1  21/118 (17.80%)  16/119 (13.45%)  4/116 (3.45%) 
Hypokalaemia † 1  8/118 (6.78%)  6/119 (5.04%)  0/116 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  15/118 (12.71%)  17/119 (14.29%)  14/116 (12.07%) 
Back pain † 1  8/118 (6.78%)  11/119 (9.24%)  8/116 (6.90%) 
Bone pain † 1  6/118 (5.08%)  2/119 (1.68%)  6/116 (5.17%) 
Myalgia † 1  6/118 (5.08%)  5/119 (4.20%)  8/116 (6.90%) 
Pain in extremity † 1  8/118 (6.78%)  12/119 (10.08%)  4/116 (3.45%) 
Nervous system disorders       
Dizziness † 1  8/118 (6.78%)  8/119 (6.72%)  7/116 (6.03%) 
Headache † 1  6/118 (5.08%)  19/119 (15.97%)  12/116 (10.34%) 
Psychiatric disorders       
Insomnia † 1  4/118 (3.39%)  8/119 (6.72%)  4/116 (3.45%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1  10/118 (8.47%)  9/119 (7.56%)  17/116 (14.66%) 
Dyspnoea † 1  6/118 (5.08%)  8/119 (6.72%)  8/116 (6.90%) 
Epistaxis † 1  9/118 (7.63%)  8/119 (6.72%)  0/116 (0.00%) 
Nasal dryness † 1  6/118 (5.08%)  2/119 (1.68%)  2/116 (1.72%) 
Skin and subcutaneous tissue disorders       
Alopecia † 1  12/118 (10.17%)  8/119 (6.72%)  2/116 (1.72%) 
Dermatitis acneiform † 1  15/118 (12.71%)  10/119 (8.40%)  2/116 (1.72%) 
Dry skin † 1  11/118 (9.32%)  11/119 (9.24%)  0/116 (0.00%) 
Nail disorder † 1  6/118 (5.08%)  6/119 (5.04%)  1/116 (0.86%) 
Palmar-plantar erythrodysaesthesia syndrome † 1  12/118 (10.17%)  10/119 (8.40%)  1/116 (0.86%) 
Pruritus † 1  9/118 (7.63%)  11/119 (9.24%)  1/116 (0.86%) 
Rash † 1  43/118 (36.44%)  33/119 (27.73%)  2/116 (1.72%) 
Rash maculo-papular † 1  6/118 (5.08%)  7/119 (5.88%)  0/116 (0.00%) 
Skin fissures † 1  7/118 (5.93%)  3/119 (2.52%)  2/116 (1.72%) 
Vascular disorders       
Hot flush † 1  3/118 (2.54%)  3/119 (2.52%)  6/116 (5.17%) 
Hypertension † 1  6/118 (5.08%)  3/119 (2.52%)  6/116 (5.17%) 
1
Term from vocabulary, MedDRA (20.1)
†
Indicates events were collected by systematic assessment
[Not Specified]
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 (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01160211    
Other Study ID Numbers: 114299
2010-019577-16 ( EudraCT Number )
CLAP016A2307 ( Other Identifier: Novartis )
First Submitted: July 1, 2010
First Posted: July 12, 2010
Results First Submitted: January 3, 2019
Results First Posted: July 15, 2019
Last Update Posted: June 30, 2022