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A Study of Pertuzumab in Combination With Trastuzumab Plus an Aromatase Inhibitor in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-Positive and Hormone Receptor-Positive Advanced Breast Cancer (PERTAIN)

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ClinicalTrials.gov Identifier: NCT01491737
Recruitment Status : Completed
First Posted : December 14, 2011
Results First Posted : June 7, 2017
Last Update Posted : October 28, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Pertuzumab
Drug: Trastuzumab
Drug: Aromatase Inhibitor
Drug: Induction Chemotherapy
Enrollment 258
Recruitment Details  
Pre-assignment Details A total of 258 participants were enrolled in the study.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling. Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Period Title: Overall Study
Started [1] 129 129
Received at Least One Dose of Study Drug [2] 127 124
Entered Follow-Up (Post-Treatment) 120 116
Completed 0 0
Not Completed 129 129
Reason Not Completed
Withdrawal by Subject             20             17
Lost to Follow-up             2             10
Death             63             57
Study Termination by Sponsor             36             36
Reason Not Specified             8             9
[1]
Intent-to-Treat (ITT) Population
[2]
Safety Population
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy Total
Hide Arm/Group Description Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling. Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling. Total of all reporting groups
Overall Number of Baseline Participants 129 129 258
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 129 participants 129 participants 258 participants
60.9  (10.85) 62.3  (11.54) 61.6  (11.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 258 participants
Female
129
 100.0%
129
 100.0%
258
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 258 participants
American Indian or Alaska Native
0
   0.0%
1
   0.8%
1
   0.4%
Asian
10
   7.8%
18
  14.0%
28
  10.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   3.1%
5
   3.9%
9
   3.5%
White
104
  80.6%
93
  72.1%
197
  76.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
11
   8.5%
12
   9.3%
23
   8.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 129 participants 258 participants
Hispanic/Latino
45
  34.9%
40
  31.0%
85
  32.9%
Chinese
0
   0.0%
0
   0.0%
0
   0.0%
Indian (Indian subcontinent)
10
   7.8%
16
  12.4%
26
  10.1%
Japanese
0
   0.0%
1
   0.8%
1
   0.4%
Mixed Ethnicity
0
   0.0%
0
   0.0%
0
   0.0%
Other
63
  48.8%
60
  46.5%
123
  47.7%
Missing
11
   8.5%
12
   9.3%
23
   8.9%
Number of Participants by Induction Chemotherapy and Prior Adjuvant Hormone Therapy   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Induction Chemotherapy - Yes Number Analyzed 75 participants 73 participants 148 participants
<12 Months Since Hormone Therapy
12
  16.0%
12
  16.4%
24
  16.2%
≥12 Months Since Hormone Therapy
24
  32.0%
23
  31.5%
47
  31.8%
No Prior Hormone Therapy
39
  52.0%
38
  52.1%
77
  52.0%
Induction Chemotherapy - No Number Analyzed 54 participants 56 participants 110 participants
<12 Months Since Hormone Therapy
12
  22.2%
12
  21.4%
24
  21.8%
≥12 Months Since Hormone Therapy
18
  33.3%
19
  33.9%
37
  33.6%
No Prior Hormone Therapy
24
  44.4%
25
  44.6%
49
  44.5%
[1]
Measure Description: Participants were stratified at randomization according to the following factors: -Chosen to receive induction chemotherapy? (Yes vs. No); -Time since adjuvant hormone therapy (<12 months vs. ≥12 months), or no prior hormone therapy.
[2]
Measure Analysis Population Description: All 258 participants who were enrolled on this study are accounted for between the induction chemotherapy categories (yes vs. no).
1.Primary Outcome
Title Progression-Free Survival (PFS)
Hide Description Progression-free survival (PFS) was defined as the time from randomization until the first radiographically documented progression of disease or death from any cause, whichever occurred first (either during study treatment or during follow-up). Progression of disease was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum of target lesion diameters must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression). Participants with no PFS events were censored at the time of the last evaluable tumor assessment. The primary analysis of PFS was planned to be performed when a total of 165 PFS events had occurred, and the final analysis after at least 60 months follow-up.
Time Frame Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population included all randomized participants.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 129 129
Median (95% Confidence Interval)
Unit of Measure: months
Primary Analysis
18.89
(14.09 to 27.66)
15.80
(11.04 to 18.56)
Final Analysis
20.63
(14.39 to 28.35)
15.80
(11.04 to 18.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments Primary Analysis. Log Rank tested the following: Null Hypothesis (H0): the distribution of the PFS time was the same in Arms A & B; The Alternative Hypothesis (H1): the distribution of the PFS time was different in Arms A & B. A Cox proportional hazards model tested the HR. If the HR of investigational arm (Arm A) compared with control arm (Arm B) with respect to PFS was assumed to be constant over time (λ) then the null (H0) and alternative hypotheses (H1) were: H0: λ =1; H1: λ ≠1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0070
Comments Test was performed at 2-sided alpha of 5%.
Method Log Rank
Comments Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.48 to 0.89
Estimation Comments Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments Final Analysis
Type of Statistical Test Other
Comments Exploratory
Statistical Test of Hypothesis P-Value 0.0059
Comments [Not Specified]
Method Log Rank
Comments Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.50 to 0.89
Estimation Comments Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) was defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication (pertuzumab, trastuzumab, AI or induction chemotherapy), and participants with no post-baseline information were censored at the date of randomization. The primary analysis of OS was planned to be performed at the same time as for PFS (when a total of 165 PFS events had occurred), and the final analysis was planned after at least 60 months follow-up for all participants.
Time Frame Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 129 129
Median (95% Confidence Interval)
Unit of Measure: Months
Primary Analysis
NA [1] 
(NA to NA)
NA [2] 
(41.40 to NA)
Final Analysis
60.16
(47.21 to 79.01)
57.17 [3] 
(45.44 to NA)
[1]
Median and lower and upper limits of the 95% confidence interval were not reached because not enough events had occurred at the time of analysis.
[2]
Median and upper limit of the 95% confidence interval were not reached because not enough events had occurred at the time of analysis.
[3]
Upper limit of 95% confidence interval was not reached because not enough events had occurred the time of analysis.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments Primary Analysis. This study was not powered for overall survival (OS), so adequately powered statistical testing for this outcome measure was not possible.
Type of Statistical Test Other
Comments Exploratory
Statistical Test of Hypothesis P-Value 0.5850
Comments [Not Specified]
Method Log Rank
Comments Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.69 to 1.91
Estimation Comments Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments Final Analysis. This study was not powered for overall survival (OS), so adequately powered statistical testing for this outcome measure was not possible.
Type of Statistical Test Other
Comments Exploratory
Statistical Test of Hypothesis P-Value 0.7833
Comments [Not Specified]
Method Log Rank
Comments Stratified log-rank test based upon Kaplan-Meier including induction chemotherapy and prior adjuvant hormone therapy stratification factors.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.73 to 1.52
Estimation Comments Hazard ratio comparing Arm A vs. B from stratified Cox proportional hazards model including stratification factors.
3.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description The overall response rate (ORR) was defined as the percentage of participants with best (confirmed) overall response (BOR) of either complete response (CR) or partial response (PR) from start of study treatment until progressive disease (PD)/recurrence or death, as assessed by the investigator according to RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters; stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participants needed to have two consecutive assessments of PR or CR at least 4 weeks apart to be a responder. Analysis of this outcome measure was only planned to occur at the time of primary analysis.
Time Frame Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. Only participants with measurable disease at baseline were included in the analysis.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 109 106
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
ORR (CR + PR)
63.3
(53.5 to 72.3)
55.7
(45.7 to 65.3)
Non-responders (SD + PD + NE)
36.7
(27.7 to 46.5)
44.3
(34.7 to 54.3)
Complete Response (CR)
7.3
(3.2 to 14.0)
0.9
(0.0 to 5.1)
Partial Response (PR)
56.0
(46.1 to 65.5)
54.7
(44.8 to 64.4)
Stable Disease (SD)
26.6
(18.6 to 35.9)
27.4
(19.1 to 36.9)
Progressive Disease (PD)
5.5
(2.0 to 11.6)
12.3
(6.7 to 20.1)
Not Evaluable (NE)
4.5
(1.5 to 10.4)
4.7
(1.5 to 10.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments ORR for Arm A vs Arm B
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2537
Comments Test was performed at 2-sided alpha of 5%. There was no multiplicity adjustment.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in ORR
Estimated Value 7.6
Confidence Interval (2-Sided) 95%
-6.0 to 21.3
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description Clinical Benefit Rate (CBR) was defined as the percentage of participants with best (confirmed) partial response (PR) or complete response (CR) or stable disease (SD) for at least 6 months. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Analysis of this outcome measure was only planned to occur at the time of primary analysis.
Time Frame Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. Only participants with measurable disease at baseline were included in the analysis.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 109 106
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
CBR (CR + PR + SD for ≥6 Months)
68.8
(59.2 to 77.3)
67.0
(57.2 to 75.8)
Complete Response (CR)
7.3
(3.2 to 14.0)
0.9
(0.0 to 5.1)
Partial Response (PR)
56.0
(46.1 to 65.5)
54.7
(44.8 to 64.4)
Stable Disease (SD) for ≥6 Months
5.5
(2.0 to 11.6)
11.3
(6.0 to 18.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments CBR for Arm A vs. Arm B
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7743
Comments Test was performed at 2-sided alpha of 5%. There was no multiplicity adjustment.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in CBR
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-11.2 to 14.8
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Duration of Response (DOR)
Hide Description Duration of response (DOR) was defined as the period from the date of initial confirmed partial response (PR) or complete response (CR) until the date of progressive disease or death from any cause. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants with no documented progression after CR or PR were censored at the last date at which they were known to have had the CR or PR, respectively. The primary analysis of DOR was planned to be performed at the same time as for PFS (when a total of 165 PFS events had occurred), and the final analysis was planned after at least 60 months follow-up for all participants.
Time Frame Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. Only participants who had measurable disease at baseline and were responders (CR or PR) were included in this analysis.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 69 61
Median (95% Confidence Interval)
Unit of Measure: months
Primary Analysis Number Analyzed 69 participants 59 participants
27.10 [1] 
(14.13 to NA)
15.11
(12.09 to 20.96)
Final Analysis Number Analyzed 69 participants 61 participants
27.40
(15.24 to 44.35)
16.36
(12.09 to 20.96)
[1]
Upper limit of the 95% confidence interval was not reached because not enough events had occurred at the time of analysis.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments Primary Analysis. Log Rank tested the following: Null Hypothesis (H0): the distribution of the DOR time was the same in Arms A & B; The Alternative Hypothesis (H1): the distribution of the DOR time was different in Arms A & B. A Cox proportional hazards model tested the HR. If the HR of investigational arm (Arm A) compared with control arm (Arm B) with respect to DOR was assumed to be constant over time (λ) then the null (H0) and alternative hypotheses (H1) were: H0: λ =1; H1: λ ≠1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0181
Comments Test was performed at 2-sided alpha of 5%.
Method Log Rank
Comments Log-rank test from unstratified analysis based upon Kaplan-Meier approach. There was no multiplicity adjustment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.36 to 0.91
Estimation Comments Hazard ratio from stratified Cox proportional hazards model including stratification factors of induction chemotherapy and prior adjuvant hormone therapy.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments Final Analysis.
Type of Statistical Test Other
Comments Exploratory
Statistical Test of Hypothesis P-Value 0.0205
Comments [Not Specified]
Method Log Rank
Comments Log-rank test from unstratified analysis based upon Kaplan-Meier approach. There was no multiplicity adjustment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.41 to 0.93
Estimation Comments Hazard ratio from stratified Cox proportional hazards model including stratification factors of induction chemotherapy and prior adjuvant hormone therapy.
6.Secondary Outcome
Title Time to Response (TTR)
Hide Description Time to Response (TTR) was defined as the time from the date of randomization to the date of first complete response (CR) or partial response (PR). According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For participants who did not have a confirmed response, a censored TTR was calculated at the date of the last adequate tumor assessment. If no tumor assessment is performed for the participant (or all post-baseline assessments are not evaluable or PD) the censoring day would be set to day 1 (date of randomization). Analysis of this outcome measure was only planned to occur at the time of primary analysis.
Time Frame Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. Only participants with measurable disease at baseline were included in this analysis.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 109 106
Median (95% Confidence Interval)
Unit of Measure: months
2.53
(2.10 to 4.37)
3.91
(2.10 to 4.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy, Arm B: Trastuzumab + AI +/- Chemotherapy
Comments Log Rank tested the following: Null Hypothesis (H0): the distribution of the TTR time was the same in Arms A & B; The Alternative Hypothesis (H1): the distribution of the TTR time was different in Arms A & B. A Cox proportional hazards model tested the HR. If the HR of investigational arm (Arm A) compared with control arm (Arm B) with respect to TTR was assumed to be constant over time (λ) then the null (H0) and alternative hypotheses (H1) were: H0: λ =1; H1: λ ≠1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5597
Comments Test was performed at 2-sided alpha of 5%.
Method Log Rank
Comments The log-rank test from unstratified analysis was based upon Kaplan-Meier approach. There was no multiplicity adjustment.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.78 to 1.57
Estimation Comments Hazard ratio from stratified Cox proportional hazards model including the induction chemotherapy and prior adjuvant hormone therapy stratification factors.
7.Secondary Outcome
Title Change From Baseline in Health-Related Quality of Life as Determined by European Quality of Life 5-Dimension (EQ-5D) Visual Analog Scale (VAS) Scores
Hide Description The EQ-5D VAS is a participant-rated questionnaire to assess health-related quality of life (QoL) in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.
Time Frame Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. The number analyzed only included those who had a non-missing assessment for a specified time point.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 129 129
Mean (Standard Deviation)
Unit of Measure: unit on a scale
Baseline (BL) - Value at Visit Number Analyzed 98 participants 101 participants
73.0  (19.34) 72.8  (18.83)
Change from BL at Cycle 3 Number Analyzed 87 participants 87 participants
3.3  (14.90) 1.9  (15.67)
Change from BL at Cycle 6 Number Analyzed 82 participants 75 participants
3.5  (18.91) 0.5  (13.63)
Change from BL at Cycle 9 Number Analyzed 68 participants 66 participants
5.3  (18.80) 2.1  (15.20)
Change from BL at Cycle 12 Number Analyzed 58 participants 52 participants
10.7  (17.91) 4.0  (15.34)
Change from BL at Cycle 15 Number Analyzed 54 participants 50 participants
9.1  (17.25) 1.4  (22.16)
Change from BL at Cycle 18 Number Analyzed 47 participants 43 participants
7.5  (12.85) 3.5  (15.76)
Change from BL at Cycle 21 Number Analyzed 44 participants 39 participants
5.8  (13.68) 3.5  (19.70)
Change from BL at Cycle 24 Number Analyzed 39 participants 38 participants
6.2  (14.30) 3.2  (16.66)
Change from BL at Cycle 27 Number Analyzed 35 participants 34 participants
7.5  (14.01) 3.9  (22.00)
Change from BL at Cycle 30 Number Analyzed 33 participants 29 participants
8.3  (14.25) 4.9  (16.98)
Change from BL at Cycle 33 Number Analyzed 34 participants 24 participants
5.1  (14.70) 4.3  (15.59)
Change from BL at Cycle 36 Number Analyzed 30 participants 21 participants
7.3  (15.19) 5.9  (15.13)
Change from BL at Cycle 39 Number Analyzed 30 participants 18 participants
8.1  (16.33) 2.4  (29.68)
Change from BL at Cycle 42 Number Analyzed 25 participants 15 participants
6.4  (19.18) 9.0  (17.55)
Change from BL at Cycle 45 Number Analyzed 22 participants 14 participants
9.7  (15.01) 9.9  (19.52)
Change from BL at Cycle 48 Number Analyzed 19 participants 13 participants
8.8  (12.50) 6.8  (17.22)
Change from BL at Cycle 51 Number Analyzed 18 participants 13 participants
7.2  (14.81) 9.1  (19.11)
Change from BL at Cycle 54 Number Analyzed 16 participants 12 participants
4.7  (23.48) 7.6  (17.85)
Change from BL at Cycle 57 Number Analyzed 16 participants 11 participants
6.8  (18.08) 10.5  (16.81)
Change from BL at Cycle 60 Number Analyzed 16 participants 11 participants
8.2  (15.88) 10.9  (18.27)
Change from BL at Cycle 63 Number Analyzed 16 participants 10 participants
4.0  (20.88) 8.8  (14.64)
Change from BL at Cycle 66 Number Analyzed 14 participants 8 participants
10.4  (16.92) 4.1  (15.69)
Change from BL at Cycle 69 Number Analyzed 13 participants 7 participants
7.5  (17.35) 5.0  (16.77)
Change from BL at Cycle 72 Number Analyzed 13 participants 8 participants
6.2  (16.10) 5.8  (16.10)
Change from BL at Cycle 75 Number Analyzed 11 participants 7 participants
8.6  (19.12) 5.1  (15.50)
Change from BL at Cycle 78 Number Analyzed 11 participants 7 participants
12.8  (17.45) 6.9  (14.58)
Change from BL at Cycle 81 Number Analyzed 11 participants 6 participants
11.5  (18.39) 8.0  (14.76)
Change from BL at Cycle 84 Number Analyzed 11 participants 6 participants
11.2  (19.71) 1.3  (18.13)
Change from BL at Cycle 87 Number Analyzed 11 participants 4 participants
11.2  (18.17) -3.0  (11.22)
Change from BL at Cycle 90 Number Analyzed 11 participants 4 participants
10.9  (18.28) -3.0  (12.36)
Change from BL at Cycle 93 Number Analyzed 11 participants 5 participants
7.1  (15.43) 6.6  (13.89)
Change from BL at Cycle 96 Number Analyzed 8 participants 5 participants
7.5  (16.04) 8.6  (12.64)
Change from BL at Cycle 99 Number Analyzed 9 participants 5 participants
4.4  (17.22) 5.6  (16.71)
Change from BL at Cycle 102 Number Analyzed 8 participants 3 participants
5.6  (16.35) 10.0  (17.32)
Change from BL at Cycle 105 Number Analyzed 8 participants 1 participants
4.4  (16.35) 0.0 [1]   (NA)
Change from BL at Cycle 108 Number Analyzed 7 participants 1 participants
4.0  (14.39) 0.0 [1]   (NA)
Change from BL at Cycle 111 Number Analyzed 4 participants 0 participants
3.3  (21.50)
Change from BL at Cycle 114 Number Analyzed 4 participants 0 participants
-1.3  (17.97)
Change from BL at Cycle 117 Number Analyzed 1 participants 0 participants
-5.0 [1]   (NA)
Change from BL at Cycle 120 Number Analyzed 1 participants 0 participants
-5.0 [1]   (NA)
[1]
Standard deviation could not be calculated using data from a single participant.
8.Secondary Outcome
Title Overview of the Number of Participants With Adverse Events, Severity Determined According to NCI-CTCAE Version 4.03
Hide Description All adverse events (AEs) occurring during the study and until the post-treatment safety follow-up visit approximately 28 days after last study medication were recorded; thereafter, only study drug-related serious adverse events (SAEs) continued to be collected. The investigator graded all AEs for severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. AEs suggestive of congestive heart failure (CHF) were identified by the SMQ (wide) "Cardiac Failure" with a status of "serious", which included the preferred terms cardiac failure, left ventricular dysfunction, and pulmonary oedema.
Time Frame From Baseline until the end of post-treatment follow-up (up to 89 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: included all participants who had received at least 1 dose of any study medication assigned to treatment arms as treated.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 127 124
Measure Type: Count of Participants
Unit of Measure: Participants
Any Adverse Event (AE) Number Analyzed 127 participants 124 participants
122
  96.1%
122
  98.4%
Any AE, Grade ≥3 Number Analyzed 127 participants 124 participants
72
  56.7%
51
  41.1%
Any Serious Adverse Event (SAE), Grade ≥3 Number Analyzed 127 participants 124 participants
35
  27.6%
22
  17.7%
Any AE, Grade 5 Number Analyzed 127 participants 124 participants
1
   0.8%
1
   0.8%
Any SAE Number Analyzed 127 participants 124 participants
46
  36.2%
28
  22.6%
SAE Related to Pertuzumab Number Analyzed 127 participants 124 participants
10
   7.9%
NA [1] 
SAE Related to Trastuzumab Number Analyzed 127 participants 124 participants
9
   7.1%
2
   1.6%
SAE Related to Docetaxel Number Analyzed 74 participants 69 participants
6
   8.1%
4
   5.8%
SAE Related to Paclitaxel Number Analyzed 74 participants 69 participants
3
   4.1%
0
   0.0%
Any AE Leading to Discontinuation of Any Treatment Number Analyzed 127 participants 124 participants
20
  15.7%
10
   8.1%
Any AE Leading to Pertuzumab Discontinuation Number Analyzed 127 participants 124 participants
16
  12.6%
NA [1] 
Any AE Leading to Trastuzumab Discontinuation Number Analyzed 127 participants 124 participants
16
  12.6%
6
   4.8%
Any AE Leading to Interruption of Any Treatment Number Analyzed 127 participants 124 participants
59
  46.5%
26
  21.0%
Any AE Leading to Pertuzumab Interruption Number Analyzed 127 participants 124 participants
44
  34.6%
NA [1] 
Any AE Leading to Trastuzumab Interruption Number Analyzed 127 participants 124 participants
48
  37.8%
16
  12.9%
Any AE Related to Pertuzumab Number Analyzed 127 participants 124 participants
82
  64.6%
NA [1] 
Any AE Related to Trastuzumab Number Analyzed 127 participants 124 participants
81
  63.8%
62
  50.0%
AE Suggestive of Congestive Heart Failure Number Analyzed 127 participants 124 participants
5
   3.9%
1
   0.8%
[1]
None of the participants in Arm B were treated with pertuzumab.
9.Secondary Outcome
Title Number of Participants Who Died Over the Course of the Study by Reported Cause of Death and Time of Death Relative to First or Last Dose of Study Treatment
Hide Description The causes of death over the course of the study, regardless of whether the death was related to study treatment, are listed by preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA), version 22.1.
Time Frame From Baseline until the end of post-treatment follow-up (up to 89 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: included all participants who had received at least 1 dose of any study medication assigned to treatment arms as treated.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 127 124
Measure Type: Count of Participants
Unit of Measure: Participants
Total Number of Deaths
62
  48.8%
57
  46.0%
Deaths Related to Any Study Treatment
0
   0.0%
0
   0.0%
Cause of Death: Cardiac Arrest
1
   0.8%
0
   0.0%
Cause of Death: Craniocerebral Injury
1
   0.8%
0
   0.0%
Cause of Death: Dyspnoea
1
   0.8%
0
   0.0%
Cause of Death: High-grade B-cell Lymphoma
1
   0.8%
0
   0.0%
Cause of Death: Sudden Death
0
   0.0%
1
   0.8%
Cause of Death: Unevaluable Event
2
   1.6%
1
   0.8%
Cause of Death: Progressive Disease
56
  44.1%
55
  44.4%
Total Deaths Within 30 Days After First Dose
0
   0.0%
0
   0.0%
Total Deaths Within 28 Days After Last Dose
1
   0.8%
2
   1.6%
Total Deaths Within 60 Days After Last Dose
2
   1.6%
4
   3.2%
10.Secondary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study
Hide Description Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. A normal LVEF ranges from 55% to 70%, as measured by echocardiogram or multiple-gated acquisition (MUGA) scan. All participants must have had a baseline LVEF of at least (≥)50% to enroll in the study; patients with clinically significant cardiovascular disease or baseline LVEF below 50% were not eligible for this study.
Time Frame Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: included all participants who had received at least 1 dose of any study medication assigned to treatment arms as treated.
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description:
Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
Overall Number of Participants Analyzed 127 124
Mean (Standard Deviation)
Unit of Measure: Percentage points of LVEF
Baseline (BL) - Absolute LVEF at Visit Number Analyzed 127 participants 123 participants
63.8  (6.23) 63.9  (6.12)
Change from BL at Cycle 3 Number Analyzed 114 participants 114 participants
-1.0  (6.25) -1.4  (6.23)
Change from BL at Cycle 6 Number Analyzed 101 participants 101 participants
-2.3  (6.66) -1.3  (6.03)
Change from BL at Cycle 9 Number Analyzed 87 participants 84 participants
-2.5  (6.80) -2.2  (6.52)
Change from BL at Cycle 12 Number Analyzed 75 participants 69 participants
-2.4  (8.05) -2.8  (6.99)
Change from BL at Cycle 15 Number Analyzed 64 participants 61 participants
-2.9  (8.67) -2.5  (6.94)
Change from BL at Cycle 18 Number Analyzed 62 participants 54 participants
-1.9  (6.42) -1.3  (6.19)
Change from BL at Cycle 21 Number Analyzed 53 participants 48 participants
-1.1  (6.01) -1.1  (6.64)
Change from BL at Cycle 24 Number Analyzed 52 participants 46 participants
-2.1  (6.82) -0.6  (6.19)
Change from BL at Cycle 27 Number Analyzed 46 participants 39 participants
-1.6  (5.05) -1.3  (5.87)
Change from BL at Cycle 30 Number Analyzed 43 participants 34 participants
-1.4  (5.20) -0.3  (6.03)
Change from BL at Cycle 33 Number Analyzed 44 participants 28 participants
-2.8  (5.60) 1.2  (6.71)
Change from BL at Cycle 36 Number Analyzed 37 participants 24 participants
-2.5  (5.50) -0.2  (5.41)
Change from BL at Cycle 39 Number Analyzed 38 participants 23 participants
-2.6  (5.72) 1.4  (4.87)
Change from BL at Cycle 42 Number Analyzed 35 participants 18 participants
-2.1  (5.91) 1.9  (6.12)
Change from BL at Cycle 45 Number Analyzed 31 participants 17 participants
-1.0  (5.54) 3.0  (5.27)
Change from BL at Cycle 48 Number Analyzed 28 participants 18 participants
-3.3  (6.56) -0.2  (7.50)
Change from BL at Cycle 51 Number Analyzed 27 participants 18 participants
-1.4  (5.82) 1.0  (4.19)
Change from BL at Cycle 54 Number Analyzed 26 participants 13 participants
-1.3  (6.17) -1.0  (6.23)
Change from BL at Cycle 57 Number Analyzed 26 participants 15 participants
-1.7  (6.43) 0.8  (5.68)
Change from BL at Cycle 60 Number Analyzed 25 participants 14 participants
-2.5  (5.54) -0.9  (3.91)
Change from BL at Cycle 63 Number Analyzed 26 participants 14 participants
-2.1  (6.10) 0.8  (5.99)
Change from BL at Cycle 66 Number Analyzed 22 participants 13 participants
-2.9  (7.80) -0.4  (5.17)
Change from BL at Cycle 69 Number Analyzed 19 participants 9 participants
-2.1  (7.23) -1.5  (7.68)
Change from BL at Cycle 72 Number Analyzed 18 participants 12 participants
-3.0  (4.97) -1.0  (5.75)
Change from BL at Cycle 75 Number Analyzed 17 participants 12 participants
-3.3  (6.59) -1.1  (6.97)
Change from BL at Cycle 78 Number Analyzed 17 participants 9 participants
-3.3  (5.58) -1.1  (7.82)
Change from BL at Cycle 81 Number Analyzed 17 participants 9 participants
-2.9  (6.83) -2.6  (6.00)
Change from BL at Cycle 84 Number Analyzed 15 participants 9 participants
-2.5  (7.66) -4.5  (3.59)
Change from BL at Cycle 87 Number Analyzed 15 participants 8 participants
-3.8  (5.76) -1.4  (5.12)
Change from BL at Cycle 90 Number Analyzed 16 participants 7 participants
-2.4  (7.69) 0.4  (6.77)
Change from BL at Cycle 93 Number Analyzed 14 participants 7 participants
-1.8  (6.57) -3.9  (6.00)
Change from BL at Cycle 96 Number Analyzed 12 participants 7 participants
-0.7  (7.45) -3.2  (5.50)
Change from BL at Cycle 99 Number Analyzed 11 participants 7 participants
-3.4  (5.78) -2.8  (8.41)
Change from BL at Cycle 102 Number Analyzed 13 participants 5 participants
-1.3  (6.12) -1.6  (9.68)
Change from BL at Cycle 105 Number Analyzed 12 participants 3 participants
-0.4  (7.05) -2.0  (12.17)
Change from BL at Cycle 108 Number Analyzed 9 participants 3 participants
-3.4  (5.32) -3.3  (8.33)
Change from BL at Cycle 111 Number Analyzed 4 participants 1 participants
-6.3  (5.91) -5.5 [1]   (NA)
Change from BL at Cycle 114 Number Analyzed 4 participants 1 participants
-4.0  (5.35) -1.4 [1]   (NA)
Change from BL at Cycle 117 Number Analyzed 1 participants 0 participants
-11.0 [1]   (NA)
Change from BL at Cycle 120 Number Analyzed 1 participants 0 participants
-11.0 [1]   (NA)
[1]
Standard deviation could not be calculated with data from a single participant.
Time Frame From Baseline until end of post-treatment follow-up (up to 89 months)
Adverse Event Reporting Description All adverse events that occurred during the study and until the post-treatment safety follow-up visit approximately 28 days after last study medication were to be recorded. Thereafter, only serious adverse events thought to be related to study drug were collected.
 
Arm/Group Title Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Hide Arm/Group Description Participants received pertuzumab at a loading dose of 840 mg followed by 420 mg along with trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling. Participants received trastuzumab at a loading dose of 8 mg/kg of body weight followed by 6 mg/kg of body weight on Day 1 or Day 2 of each 3-weekly cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death, or the predefined end of study whichever occurred first. Participants also received an aromatase inhibitor (AI), orally as per product labeling (anastrozole: 1 mg once daily or letrozole: 2.5 mg once daily). Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period were to receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective product labeling.
All-Cause Mortality
Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   63/129 (48.84%)      57/129 (44.19%)    
Hide Serious Adverse Events
Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   46/127 (36.22%)      28/124 (22.58%)    
Blood and lymphatic system disorders     
Febrile neutropenia  1  4/127 (3.15%)  4 2/124 (1.61%)  2
Neutropenia  1  1/127 (0.79%)  1 1/124 (0.81%)  1
Cardiac disorders     
Atrial fibrillation  1  2/127 (1.57%)  3 0/124 (0.00%)  0
Cardiac failure  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Left ventricular dysfunction  1  4/127 (3.15%)  4 0/124 (0.00%)  0
Mitral valve disease  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Myocardial ischaemia  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Sinus tachycardia  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Myocardial infarction  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Endocrine disorders     
Adrenal haemorrhage  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Abdominal pain  1  1/127 (0.79%)  1 1/124 (0.81%)  1
Constipation  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Diarrhoea  1  2/127 (1.57%)  2 1/124 (0.81%)  1
Vomiting  1  2/127 (1.57%)  3 1/124 (0.81%)  1
Large intestinal obstruction  1  1/127 (0.79%)  1 0/124 (0.00%)  0
General disorders     
Chest pain  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Pyrexia  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Sudden death  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Hepatobiliary disorders     
Cholecystitis  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Immune system disorders     
Anaphylactic shock  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Contrast media allergy  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Hypersensitivity  1  3/127 (2.36%)  3 0/124 (0.00%)  0
Infections and infestations     
Abscess  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Colonic abscess  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Device related infection  1  0/127 (0.00%)  0 2/124 (1.61%)  2
Erysipelas  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Escherichia urinary tract infection  1  0/127 (0.00%)  0 1/124 (0.81%)  2
Gastroenteritis  1  3/127 (2.36%)  3 0/124 (0.00%)  0
Gastroenteritis viral  1  1/127 (0.79%)  1 1/124 (0.81%)  1
Infection  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Mastitis  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Neutropenic sepsis  1  1/127 (0.79%)  1 1/124 (0.81%)  1
Pneumonia  1  6/127 (4.72%)  7 1/124 (0.81%)  1
Respiratory tract infection  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Sepsis  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Tooth infection  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Vascular device infection  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Injury, poisoning and procedural complications     
Femoral neck fracture  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Fracture  1  1/127 (0.79%)  1 1/124 (0.81%)  1
Humerus fracture  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Post procedural haematoma  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Spinal fracture  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Fall  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Hyperuricaemia  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Hyponatraemia  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Dehydration  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Pain in extremity  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Pathological fracture  1  1/127 (0.79%)  1 1/124 (0.81%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Adenoid cystic carcinoma of salivary gland  1  0/127 (0.00%)  0 1/124 (0.81%)  1
High-grade B-cell lymphoma  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Cancer pain  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Lung neoplasm  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Transitional cell carcinoma  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Tumour exudation  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Nervous system disorders     
Hypoglycaemic coma  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Spinal cord compression  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Psychiatric disorders     
Depression  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Confusional state  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Chronic obstructive pulmonary disease  1  2/127 (1.57%)  2 0/124 (0.00%)  0
Dyspnoea  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Pleural effusion  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Pneumonitis  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Pulmonary embolism  1  1/127 (0.79%)  1 1/124 (0.81%)  1
Pulmonary oedema  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Painful respiration  1  1/127 (0.79%)  1 0/124 (0.00%)  0
Surgical and medical procedures     
Colostomy closure  1  0/127 (0.00%)  0 1/124 (0.81%)  1
Vascular disorders     
Haematoma  1  1/127 (0.79%)  1 0/124 (0.00%)  0
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Arm B: Trastuzumab + AI +/- Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   120/127 (94.49%)      116/124 (93.55%)    
Blood and lymphatic system disorders     
Anaemia  1  28/127 (22.05%)  53 18/124 (14.52%)  30
Neutropenia  1  11/127 (8.66%)  14 13/124 (10.48%)  23
Eye disorders     
Lacrimation increased  1  9/127 (7.09%)  9 7/124 (5.65%)  8
Gastrointestinal disorders     
Abdominal pain  1  10/127 (7.87%)  11 16/124 (12.90%)  18
Abdominal pain upper  1  12/127 (9.45%)  17 6/124 (4.84%)  6
Constipation  1  18/127 (14.17%)  27 19/124 (15.32%)  25
Diarrhoea  1  70/127 (55.12%)  213 45/124 (36.29%)  88
Dyspepsia  1  8/127 (6.30%)  9 9/124 (7.26%)  11
Nausea  1  47/127 (37.01%)  68 34/124 (27.42%)  56
Stomatitis  1  17/127 (13.39%)  24 11/124 (8.87%)  22
Vomiting  1  31/127 (24.41%)  42 21/124 (16.94%)  33
Haemorrhoids  1  7/127 (5.51%)  7 2/124 (1.61%)  2
General disorders     
Asthenia  1  39/127 (30.71%)  76 32/124 (25.81%)  77
Chest Pain  1  9/127 (7.09%)  11 9/124 (7.26%)  11
Chills  1  8/127 (6.30%)  8 7/124 (5.65%)  8
Fatigue  1  21/127 (16.54%)  33 25/124 (20.16%)  43
Influenza like illness  1  10/127 (7.87%)  17 7/124 (5.65%)  10
Mucosal inflammation  1  14/127 (11.02%)  20 13/124 (10.48%)  15
Oedema peripheral  1  34/127 (26.77%)  53 23/124 (18.55%)  34
Pyrexia  1  17/127 (13.39%)  22 13/124 (10.48%)  14
Infections and infestations     
Influenza  1  6/127 (4.72%)  10 7/124 (5.65%)  12
Nasopharyngitis  1  13/127 (10.24%)  21 7/124 (5.65%)  8
Upper respiratory tract infection  1  13/127 (10.24%)  36 15/124 (12.10%)  23
Urinary tract infection  1  17/127 (13.39%)  25 16/124 (12.90%)  20
Paronychia  1  7/127 (5.51%)  12 3/124 (2.42%)  6
Investigations     
Ejection fraction decreased  1  13/127 (10.24%)  19 8/124 (6.45%)  9
Weight decreased  1  14/127 (11.02%)  16 11/124 (8.87%)  12
Weight increased  1  11/127 (8.66%)  13 5/124 (4.03%)  10
Metabolism and nutrition disorders     
Decreased appetite  1  23/127 (18.11%)  27 10/124 (8.06%)  14
Hyperglycaemia  1  8/127 (6.30%)  17 5/124 (4.03%)  9
Musculoskeletal and connective tissue disorders     
Arthralgia  1  38/127 (29.92%)  60 31/124 (25.00%)  49
Back pain  1  23/127 (18.11%)  29 21/124 (16.94%)  27
Bone pain  1  16/127 (12.60%)  25 10/124 (8.06%)  12
Muscle spasms  1  14/127 (11.02%)  17 5/124 (4.03%)  6
Musculoskeletal chest pain  1  11/127 (8.66%)  13 4/124 (3.23%)  6
Musculoskeletal pain  1  11/127 (8.66%)  11 6/124 (4.84%)  8
Myalgia  1  12/127 (9.45%)  16 9/124 (7.26%)  9
Pain in extremity  1  22/127 (17.32%)  44 16/124 (12.90%)  23
Nervous system disorders     
Dizziness  1  21/127 (16.54%)  32 12/124 (9.68%)  12
Headache  1  22/127 (17.32%)  33 14/124 (11.29%)  24
Neuropathy peripheral  1  18/127 (14.17%)  26 17/124 (13.71%)  19
Paraesthesia  1  13/127 (10.24%)  19 11/124 (8.87%)  13
Peripheral sensory neuropathy  1  10/127 (7.87%)  12 9/124 (7.26%)  9
Psychiatric disorders     
Anxiety  1  14/127 (11.02%)  15 5/124 (4.03%)  6
Depression  1  13/127 (10.24%)  14 5/124 (4.03%)  6
Insomnia  1  15/127 (11.81%)  18 18/124 (14.52%)  23
Renal and urinary disorders     
Dysuria  1  9/127 (7.09%)  14 2/124 (1.61%)  4
Respiratory, thoracic and mediastinal disorders     
Cough  1  25/127 (19.69%)  36 18/124 (14.52%)  27
Dyspnoea  1  20/127 (15.75%)  22 13/124 (10.48%)  17
Epistaxis  1  14/127 (11.02%)  18 13/124 (10.48%)  20
Skin and subcutaneous tissue disorders     
Alopecia  1  38/127 (29.92%)  40 40/124 (32.26%)  50
Dry skin  1  8/127 (6.30%)  10 6/124 (4.84%)  7
Nail disorder  1  9/127 (7.09%)  13 5/124 (4.03%)  7
Pruritus  1  20/127 (15.75%)  42 14/124 (11.29%)  19
Rash  1  23/127 (18.11%)  35 12/124 (9.68%)  17
Vascular disorders     
Hot flush  1  9/127 (7.09%)  14 9/124 (7.26%)  17
Hypertension  1  22/127 (17.32%)  54 24/124 (19.35%)  65
Lymphoedema  1  7/127 (5.51%)  10 5/124 (4.03%)  5
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01491737    
Other Study ID Numbers: MO27775
2011-002132-10 ( EudraCT Number )
First Submitted: December 6, 2011
First Posted: December 14, 2011
Results First Submitted: May 11, 2017
Results First Posted: June 7, 2017
Last Update Posted: October 28, 2020