Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel

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: NCT02586025
Recruitment Status : Active, not recruiting
First Posted : October 26, 2015
Results First Posted : January 3, 2019
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: FEC Chemotherapy
Procedure: Surgery
Drug: Docetaxel
Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab
Enrollment 329
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days). Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Period Title: Neoadjuvant Treatment
Started [1] 219 110
Received at Least One Dose of Study Drug [2] 218 110
Completed Neoadjuvant Treatment 214 108
Underwent Surgery 210 105
Completed 208 103
Not Completed 11 7
Reason Not Completed
Did Not Receive Study Drug             1             0
Death             1             0
Adverse Event             1             0
Withdrawal by Subject             4             3
Physician Decision             2             1
Progressive Disease             2             3
[1]
Intent-to-Treat (ITT) Population
[2]
Safety Evaluable Population
Period Title: Adjuvant Treatment
Started 208 103
Started Adjuvant FEC Treatment 208 103
Started Adjuvant HER2 Treatment 204 99
Completed [1] 69 34
Not Completed 139 69
Reason Not Completed
Remain in Adjuvant Treatment             133             61
Withdrawal by Subject             5             3
Physician Decision             0             1
Recurrent Disease             1             4
[1]
Completed Adjuvant HER2 Treatment
Period Title: Treatment-Free Follow-Up
Started [1] 59 38
Completed 3 3
Not Completed 56 35
Reason Not Completed
Remain in Treatment-Free Follow-Up             56             35
[1]
Includes those who discontinued from neoadjuvant and/or adjuvant treatment but remain on study
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel Total
Hide Arm/Group Description Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days). Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days). Total of all reporting groups
Overall Number of Baseline Participants 219 110 329
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 219 participants 110 participants 329 participants
48.4  (9.7) 49.5  (9.1) 48.8  (9.5)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 110 participants 329 participants
<40 years old
40
  18.3%
18
  16.4%
58
  17.6%
40-49 years old
75
  34.2%
40
  36.4%
115
  35.0%
50-64 years old
96
  43.8%
44
  40.0%
140
  42.6%
≥65 years old
8
   3.7%
8
   7.3%
16
   4.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 110 participants 329 participants
Female
219
 100.0%
110
 100.0%
329
 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 219 participants 110 participants 329 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
219
 100.0%
110
 100.0%
329
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Disease Category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 110 participants 329 participants
Early Stage
152
  69.4%
77
  70.0%
229
  69.6%
Locally Advanced
67
  30.6%
33
  30.0%
100
  30.4%
[1]
Measure Analysis Population Description: ITT Population
Hormone Receptor Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 110 participants 329 participants
Estrogen and Progesterone Negative
105
  47.9%
54
  49.1%
159
  48.3%
Estrogen and/or Progesterone Positive
114
  52.1%
56
  50.9%
170
  51.7%
Baseline LVEF value   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage points of LVEF
Number Analyzed 218 participants 110 participants 328 participants
66.41  (4.93) 66.03  (5.19) 66.28  (5.01)
[1]
Measure 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.
[2]
Measure Analysis Population Description: Safety Evaluable Population; only participants who received at least one dose of study drug are included.
1.Primary Outcome
Title Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC)
Hide Description This tpCR was assessed by the independent review committee (IRC). tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system). The analysis was based on the Intent-to-Treat (ITT) population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.
Time Frame At surgery (Cycle 4 Days 22-35)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 219 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
39.3
(32.76 to 46.08)
21.8
(14.51 to 30.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pertuzumab, Trastuzumab, Docetaxel, Placebo, Trastuzumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments Two-sided significance level of 5%
Method Cochran-Mantel-Haenszel
Comments Stratified by disease category (early-stage and locally advanced) and hormone-receptor status (positive for ER and/or PgR or negative for both)
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 17.45
Confidence Interval (2-Sided) 95%
6.89 to 28.01
Estimation Comments Pertuzumab, Trastuzumab, Docetaxel arm minus Placebo, Trastuzumab, Docetaxel arm. Approximate 95% CI for difference of two rates using Hauck-Anderson method.
2.Secondary Outcome
Title Percentage of Participants With tpCR as Assessed by the Local Pathologist
Hide Description This tpCR was assessed by the local pathologist. tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system). The analysis was based on the Intent-to-Treat (ITT) population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.
Time Frame At surgery (Cycle 4 Days 22-35)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 219 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
39.3
(32.76 to 46.08)
20.9
(13.74 to 29.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pertuzumab, Trastuzumab, Docetaxel, Placebo, Trastuzumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments Two-sided significance level of 5%
Method Cochran-Mantel-Haenszel
Comments Stratified by disease category (early-stage and locally advanced) and hormone-receptor status (positive for ER and/or PgR or negative for both)
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 18.36
Confidence Interval (2-Sided) 95%
7.89 to 28.83
Estimation Comments Pertuzumab, Trastuzumab, Docetaxel arm minus Placebo, Trastuzumab, Docetaxel arm. Approximate 95% CI for difference of two rates using Hauck-Anderson method.
3.Secondary Outcome
Title Percentage of Participants With Breast Pathologic Complete Response (bpCR), Defined as ypT0/is According to the American Joint Committee on Cancer Staging System as Assessed by the IRC
Hide Description This bpCR was assessed by the IRC. bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system). The analysis was based on the Intent-to-Treat (ITT) population with participants grouped by the treatment assigned at the time of randomization. Participants whose bpCR assessment was missing or invalid were counted as not achieving bpCR. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.
Time Frame At surgery (Cycle 4 Days 22-35)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 219 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
42.0
(35.39 to 48.85)
23.6
(16.06 to 32.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pertuzumab, Trastuzumab, Docetaxel, Placebo, Trastuzumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments Two-sided significance level of 5%
Method Cochran-Mantel-Haenszel
Comments Stratified by disease category (early-stage and locally advanced) and hormone-receptor status (positive for ER and/or PgR or negative for both)
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 18.37
Confidence Interval (2-Sided) 95%
7.60 to 29.15
Estimation Comments Pertuzumab, Trastuzumab, Docetaxel arm minus Placebo, Trastuzumab, Docetaxel arm. Approximate 95% CI for difference of two rates using Hauck-Anderson method.
4.Secondary Outcome
Title Percentage of Participants With bpCR as Assessed by the Local Pathologist
Hide Description This bpCR was assessed by the local pathologist. bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is in accordance with current AJCC staging system). The analysis was based on the Intent-to-Treat (ITT) population with participants grouped by the treatment assigned at the time of randomization. Participants whose bpCR assessment was missing or invalid were counted as not achieving bpCR. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.
Time Frame At surgery (Cycle 4 Days 22-35)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 219 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.6
(34.95 to 48.39)
22.7
(15.28 to 31.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pertuzumab, Trastuzumab, Docetaxel, Placebo, Trastuzumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments Two-sided significance level of 5%
Method Cochran-Mantel-Haenszel
Comments Stratified by disease category (early-stage and locally advanced) and hormone-receptor status (positive for ER and/or PgR or negative for both)
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 18.83
Confidence Interval (2-Sided) 95%
8.14 to 29.51
Estimation Comments Pertuzumab, Trastuzumab, Docetaxel arm minus Placebo, Trastuzumab, Docetaxel arm. Approximate 95% CI for difference of two rates using Hauck-Anderson method.
5.Secondary Outcome
Title Percentage of Participants With Complete Response, Partial Response, Stable Disease, or Progressive Disease During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Hide Description Clinical responses that include the percentage of participants with a Complete Response, Partial Response, Stable Disease, or Progressive Disease were determined by the investigator during Cycles 1‒4 (prior to surgery) on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Only participants with measurable disease at baseline were included in the analysis. The analysis was based on the Intent-to-Treat (ITT) population with participants grouped by the treatment assigned at the time of randomization. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.
Time Frame At surgery (Cycle 4 Days 22-35)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 219 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Complete Response
11.0
(7.15 to 15.87)
10.0
(5.10 to 17.19)
Partial Response
77.6
(71.52 to 82.97)
68.2
(58.62 to 76.74)
Stable Disease
8.2
(4.94 to 12.68)
19.1
(12.22 to 27.69)
Progressive Disease
0.5
(0.01 to 2.52)
1.8
(0.22 to 6.41)
Missing or Unevaluable
2.7 [1] 
(NA to NA)
0.9 [1] 
(NA to NA)
[1]
95% confidence intervals were only calculated for clinical responses.
6.Secondary Outcome
Title Percentage of Participants With an Objective Response (Complete or Partial Response) During Cycles 1-4, According to RECIST Version 1.1
Hide Description An objective response was defined as the percentage of participants who achieved a complete response or partial response as the best tumor response during the neoadjuvant period (that is, during Cycles 1‒4 prior to surgery), as determined by the investigator on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. No confirmation was required for objective response. Only participants with measurable disease at baseline were included in the analysis. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.
Time Frame At surgery (Cycle 4 Days 22-35)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 219 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
88.6
(83.61 to 92.47)
78.2
(69.30 to 85.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pertuzumab, Trastuzumab, Docetaxel, Placebo, Trastuzumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0125
Comments Two-sided significance level of 5%
Method Cochran-Mantel-Haenszel
Comments Stratified by disease category (early-stage and locally advanced) and hormone-receptor status (positive for ER and/or PgR or negative for both)
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 10.40
Confidence Interval (2-Sided) 95%
1.12 to 19.69
Estimation Comments Pertuzumab, Trastuzumab, Docetaxel arm minus Placebo, Trastuzumab, Docetaxel arm
7.Secondary Outcome
Title Kaplan-Meier Estimate of the Percentage of Participants With 3 Years of Event-Free Survival
Hide Description The Kaplan-Meier approach will be used to estimate the percentage of participants with 3 years of event-free survival (EFS). EFS is defined as the time from randomization to the first documentation of one of the following events: Disease progression (before surgery) as determined by the investigator with use of RECIST v1.1 Any evidence of contralateral disease in situ was not identified as progressive disease; Disease recurrence (local, regional, distant, or contralateral) after surgery; Death from any cause. After treatment completion/discontinuation, follow-up data will be collected every 3 months for 1 year and then every 6 months thereafter, until disease progression or recurrence or until 5 years after randomization of the last participant, whichever occurs first. Participants who do not have an EFS event at the time of the analysis are planned to be censored as of the date they are last known to be alive and event-free.
Time Frame From Baseline to EFS event or date last known to be alive and event-free (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. At the time of the clinical cut-off date (23 October 2017) for the primary analysis, EFS data were not mature and were not yet analyzed. The collection of survival follow-up data is ongoing and results will be analyzed and reported upon completion of the study.
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Kaplan-Meier Estimate of the Percentage of Participants With 3 Years of Disease-Free Survival
Hide Description The Kaplan-Meier approach will be used to estimate the percentage of participants with 3 years of disease-free survival (DFS). DFS was defined as the time from first date of no disease (i.e., date of surgery) to first documentation of one of the following events: Disease recurrence (local, regional, distant, or contralateral) after surgery. Any evidence of contralateral disease in situ was not identified as disease recurrence; Death from any cause. After treatment completion/discontinuation, follow-up data will be collected every 3 months for 1 year and then every 6 months thereafter, until disease progression or recurrence or until 5 years after randomization of the last participant, whichever occurs first. Participants were considered to be disease-free if they underwent surgery and no recurrence of disease was reported thereafter. Data from participants who do not have an event at analysis are planned to be censored as of the date they are last known to be alive and event-free.
Time Frame From surgery to DFS event or date last known to be alive and event-free (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants who underwent surgery are planned to be included in the analysis. At the time of the clinical cut-off date (23 October 2017) for the primary analysis, DFS data were not mature and were not yet analyzed. The collection of survival follow-up data is ongoing and results will be analyzed and reported upon completion of the study.
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Kaplan-Meier Estimate of the Percentage of Participants With 3 Years of Overall Survival
Hide Description The Kaplan-Meier approach will be used to estimate the percentage of participants with 3 years of overall survival (OS). OS was defined as the time from randomization to death from any cause. After treatment completion/discontinuation, follow-up data will be collected every 3 months for 1 year and then every 6 months thereafter, until disease progression or recurrence or until 5 years after randomization of the last participant, whichever occurs first. Data from participants who are alive at the time of the analysis are planned to be censored as of the last date they were known to be alive.
Time Frame From Baseline to OS event or date last known to be alive (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. At the time of the clinical cut-off date (23 October 2017) for the primary analysis, OS data were not mature and were not yet analyzed. The collection of survival follow-up data is ongoing and results will be analyzed and reported upon completion of the study.
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Percentage of Participants With At Least One Adverse Event During the Neoadjuvant Treatment Period
Hide Description The percentage of participants who experienced at least one adverse event during the neoadjuvant period is reported here. The neoadjuvant treatment period began after randomization upon receiving the first dose of any of the neoadjuvant study medications and ended before receiving the first dose of adjuvant study treatment. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.
Time Frame Baseline up to end of Cycle 4 (1 cycle = 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Evaluable Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 218 110
Measure Type: Number
Unit of Measure: percentage of participants
97.7 96.4
11.Secondary Outcome
Title Percentage of Participants With At Least One Adverse Event During the Adjuvant Treatment Period
Hide Description The percentage of participants who experienced at least one adverse event during the adjuvant period is reported here. The adjuvant treatment period began after primary surgery, upon receiving the first dose of any of the adjuvant study medications. It ended 42 days after the last dose of adjuvant study treatment upon treatment completion or discontinuation. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery. At the clinical cut-off date for the primary analysis (23-Oct-2017), the majority of participants had not completed the adjuvant treatment. Limited data were collected during the adjuvant period; full data will be reported at study completion.
Time Frame From Cycle 5 up to Cycle 20 (1 cycle = 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Evaluable Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 218 110
Measure Type: Number
Unit of Measure: percentage of participants
96.6 96.1
12.Secondary Outcome
Title Percentage of Participants With At Least One Adverse Event During the Treatment-Free Follow-Up Period
Hide Description The percentage of participants who experienced at least one adverse event during the treatment-free follow-up period is reported here. The treatment-free follow-up period started the day after the end of the overall study treatment period and continued until disease progression or recurrence or until 5 years after randomization of the last patient, whichever occurred first. At the clinical cut-off date for the primary analysis (23-Oct-2017), limited data were collected during the treatment-free follow-up period; full data will be reported at study completion.
Time Frame From end of overall study treatment until disease progression or recurrence (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Evaluable Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 218 110
Measure Type: Number
Unit of Measure: percentage of participants
0 0
13.Secondary Outcome
Title Percentage of Participants Who Experienced a Primary Cardiac Event
Hide Description A primary cardiac event is defined as heart failure (New York Heart Association [NYHA] Class III or NYHA Class IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction points from baseline and to below 50%.
Time Frame From Baseline until end of study (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Evaluable Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 218 110
Measure Type: Number
Unit of Measure: percentage of participants
0 0
14.Secondary Outcome
Title Percentage of Participants Who Experienced a Secondary Cardiac Event
Hide Description A secondary cardiac event is defined as an asymptomatic or mildly symptomatic (NYHA Class II) drop in left ventricular ejection fraction (LVEF) by multiple-gated acquisition (MUGA) scan or echocardiogram confirmed by a second LVEF assessment within approximately 3 weeks showing also a documented drop. A significant LVEF drop is defined as an absolute decrease of at least 10 points below the baseline measurement and to below 50%.
Time Frame From Baseline until end of study (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Evaluable Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 218 110
Measure Type: Number
Unit of Measure: percentage of participants
0 0
15.Secondary Outcome
Title Maximum Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
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 (preferred) or multiple-gated acquisition (MUGA) scan. The same method should be used throughout the study for each participant and preferably performed and evaluated by the same assessor. Here, we report the maximum change from baseline in LVEF at any point during the study.
Time Frame Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Evaluable Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 218 110
Mean (Standard Deviation)
Unit of Measure: percentage points of LVEF
-5.06  (5.18) -4.58  (5.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pertuzumab, Trastuzumab, Docetaxel, Placebo, Trastuzumab, Docetaxel
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-1.69 to 0.73
Estimation Comments Pertuzumab, Trastuzumab, Docetaxel arm minus Placebo, Trastuzumab, Docetaxel arm
16.Secondary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
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 (preferred) or multiple-gated acquisition (MUGA) scan. The same method should be used throughout the study for each participant and preferably performed and evaluated by the same assessor. Here, we report the change from baseline in LVEF over time.
Time Frame Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Evaluable Population
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description:
Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days).
Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
Overall Number of Participants Analyzed 218 110
Mean (95% Confidence Interval)
Unit of Measure: percentage points of LVEF
Cycle 2 Day 1 Number Analyzed 213 participants 107 participants
-0.62
(-1.35 to 0.11)
0.24
(-0.94 to 1.42)
Cycle 4 Day 1 Number Analyzed 210 participants 107 participants
-1.00
(-1.71 to -0.29)
0.08
(-1.05 to 1.22)
Cycle 5 Day 1 Number Analyzed 202 participants 101 participants
-0.95
(-1.68 to -0.21)
0.11
(-1.09 to 1.31)
Cycle 8 Day 1 Number Analyzed 194 participants 97 participants
-1.62
(-2.44 to -0.80)
-1.18
(-2.30 to -0.05)
Cycle 11 Day 1 Number Analyzed 186 participants 88 participants
-1.35
(-2.15 to -0.56)
-0.55
(-1.84 to 0.75)
Cycle 20 Day 1 Number Analyzed 58 participants 31 participants
-1.07
(-2.59 to 0.46)
-1.06
(-2.82 to 0.69)
Time Frame From baseline to clinical cut-off date (23-Oct-2017) for primary analysis (1 year, 7 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Hide Arm/Group Description Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) for 3 cycles (1 cycle = 21 days): trastuzumab and pertuzumab for up to 13 cycles (1 cycle = 21 days). Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy for 3 cycles (1 cycle = 21 days): trastuzumab and placebo for up to 13 cycles (1 cycle =21 days).
All-Cause Mortality
Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   1/218 (0.46%)   0/110 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   35/218 (16.06%)   14/110 (12.73%) 
Blood and lymphatic system disorders     
Anaemia  1  1/218 (0.46%)  0/110 (0.00%) 
Bone marrow failure  1  3/218 (1.38%)  0/110 (0.00%) 
Febrile neutropenia  1  9/218 (4.13%)  3/110 (2.73%) 
Haemorrhagic anaemia  1  0/218 (0.00%)  1/110 (0.91%) 
Lymphadenitis  1  0/218 (0.00%)  1/110 (0.91%) 
Neutropenia  1  1/218 (0.46%)  0/110 (0.00%) 
Thrombocytopenia  1  1/218 (0.46%)  0/110 (0.00%) 
Cardiac disorders     
Palpitations  1  1/218 (0.46%)  0/110 (0.00%) 
Ventricular arrhythmia  1  1/218 (0.46%)  0/110 (0.00%) 
Ventricular fibrillation  1  0/218 (0.00%)  1/110 (0.91%) 
Gastrointestinal disorders     
Diarrhoea  1  2/218 (0.92%)  0/110 (0.00%) 
Haemorrhoids  1  1/218 (0.46%)  0/110 (0.00%) 
Pancreatitis acute  1  1/218 (0.46%)  0/110 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/218 (0.46%)  0/110 (0.00%) 
Vomiting  1  2/218 (0.92%)  0/110 (0.00%) 
General disorders     
Chest discomfort  1  0/218 (0.00%)  1/110 (0.91%) 
Fatigue  1  1/218 (0.46%)  0/110 (0.00%) 
Hepatobiliary disorders     
Liver disorder  1  2/218 (0.92%)  0/110 (0.00%) 
Liver injury  1  0/218 (0.00%)  1/110 (0.91%) 
Immune system disorders     
Anaphylactic shock  1  0/218 (0.00%)  1/110 (0.91%) 
Infections and infestations     
Bacteraemia  1  2/218 (0.92%)  0/110 (0.00%) 
Device related infection  1  0/218 (0.00%)  1/110 (0.91%) 
Herpes zoster  1  0/218 (0.00%)  1/110 (0.91%) 
Lung abscess  1  1/218 (0.46%)  0/110 (0.00%) 
Lung infection  1  1/218 (0.46%)  1/110 (0.91%) 
Pneumonia  1  2/218 (0.92%)  0/110 (0.00%) 
Postoperative wound infection  1  1/218 (0.46%)  0/110 (0.00%) 
Sepsis  1  1/218 (0.46%)  0/110 (0.00%) 
Skin infection  1  0/218 (0.00%)  1/110 (0.91%) 
Urinary tract infection  1  2/218 (0.92%)  1/110 (0.91%) 
Wound infection  1  1/218 (0.46%)  0/110 (0.00%) 
Injury, poisoning and procedural complications     
Vascular access complication  1  1/218 (0.46%)  0/110 (0.00%) 
Musculoskeletal and connective tissue disorders     
Chest wall necrosis  1  1/218 (0.46%)  0/110 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Papillary thyroid cancer  1  0/218 (0.00%)  1/110 (0.91%) 
Nervous system disorders     
Dizziness  1  1/218 (0.46%)  0/110 (0.00%) 
Syncope  1  1/218 (0.46%)  0/110 (0.00%) 
Transient ischaemic attack  1  1/218 (0.46%)  0/110 (0.00%) 
Psychiatric disorders     
Completed suicide  1  1/218 (0.46%)  0/110 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Lung cyst  1  0/218 (0.00%)  1/110 (0.91%) 
Pulmonary embolism  1  1/218 (0.46%)  0/110 (0.00%) 
Skin and subcutaneous tissue disorders     
Drug eruption  1  1/218 (0.46%)  0/110 (0.00%) 
Urticaria  1  1/218 (0.46%)  0/110 (0.00%) 
Vascular disorders     
Lymphorrhoea  1  1/218 (0.46%)  0/110 (0.00%) 
1
Term from vocabulary, MedDRA version 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pertuzumab, Trastuzumab, Docetaxel Placebo, Trastuzumab, Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   217/218 (99.54%)   108/110 (98.18%) 
Blood and lymphatic system disorders     
Anaemia  1  71/218 (32.57%)  36/110 (32.73%) 
Leukopenia  1  132/218 (60.55%)  66/110 (60.00%) 
Neutropenia  1  152/218 (69.72%)  70/110 (63.64%) 
Thrombocytopenia  1  29/218 (13.30%)  17/110 (15.45%) 
Gastrointestinal disorders     
Abdominal discomfort  1  11/218 (5.05%)  3/110 (2.73%) 
Abdominal pain upper  1  10/218 (4.59%)  8/110 (7.27%) 
Constipation  1  25/218 (11.47%)  11/110 (10.00%) 
Diarrhoea  1  85/218 (38.99%)  19/110 (17.27%) 
Mouth ulceration  1  30/218 (13.76%)  11/110 (10.00%) 
Nausea  1  83/218 (38.07%)  39/110 (35.45%) 
Stomatitis  1  7/218 (3.21%)  7/110 (6.36%) 
Vomiting  1  35/218 (16.06%)  12/110 (10.91%) 
General disorders     
Asthenia  1  18/218 (8.26%)  7/110 (6.36%) 
Chills  1  12/218 (5.50%)  3/110 (2.73%) 
Fatigue  1  26/218 (11.93%)  16/110 (14.55%) 
Malaise  1  13/218 (5.96%)  5/110 (4.55%) 
Oedema peripheral  1  10/218 (4.59%)  8/110 (7.27%) 
Pyrexia  1  37/218 (16.97%)  13/110 (11.82%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  16/218 (7.34%)  7/110 (6.36%) 
Infections and infestations     
Nasopharyngitis  1  15/218 (6.88%)  4/110 (3.64%) 
Upper respiratory tract infection  1  51/218 (23.39%)  11/110 (10.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  11/218 (5.05%)  3/110 (2.73%) 
Procedural pain  1  12/218 (5.50%)  5/110 (4.55%) 
Radiation skin injury  1  22/218 (10.09%)  4/110 (3.64%) 
Investigations     
Alanine aminotransferase increased  1  61/218 (27.98%)  40/110 (36.36%) 
Aspartate aminotransferase increased  1  50/218 (22.94%)  33/110 (30.00%) 
Blood cholesterol increased  1  1/218 (0.46%)  6/110 (5.45%) 
Blood triglycerides increased  1  2/218 (0.92%)  7/110 (6.36%) 
Blood uric acid increased  1  2/218 (0.92%)  7/110 (6.36%) 
Gamma-glutamyltransferase increased  1  6/218 (2.75%)  7/110 (6.36%) 
Low density lipoprotein increased  1  3/218 (1.38%)  9/110 (8.18%) 
Metabolism and nutrition disorders     
Decreased appetite  1  37/218 (16.97%)  13/110 (11.82%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  14/218 (6.42%)  6/110 (5.45%) 
Bone pain  1  15/218 (6.88%)  8/110 (7.27%) 
Myalgia  1  14/218 (6.42%)  8/110 (7.27%) 
Pain in extremity  1  13/218 (5.96%)  4/110 (3.64%) 
Nervous system disorders     
Dizziness  1  19/218 (8.72%)  9/110 (8.18%) 
Headache  1  15/218 (6.88%)  6/110 (5.45%) 
Hypoaesthesia  1  13/218 (5.96%)  7/110 (6.36%) 
Neuropathy peripheral  1  12/218 (5.50%)  6/110 (5.45%) 
Psychiatric disorders     
Insomnia  1  23/218 (10.55%)  14/110 (12.73%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  20/218 (9.17%)  8/110 (7.27%) 
Epistaxis  1  11/218 (5.05%)  0/110 (0.00%) 
Oropharyngeal pain  1  18/218 (8.26%)  9/110 (8.18%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  114/218 (52.29%)  56/110 (50.91%) 
Pruritus  1  14/218 (6.42%)  6/110 (5.45%) 
Rash  1  24/218 (11.01%)  19/110 (17.27%) 
Rash maculo-papular  1  12/218 (5.50%)  1/110 (0.91%) 
Skin hyperpigmentation  1  4/218 (1.83%)  7/110 (6.36%) 
Vascular disorders     
Hypertension  1  6/218 (2.75%)  6/110 (5.45%) 
1
Term from vocabulary, MedDRA version 20.1
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
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02586025     History of Changes
Other Study ID Numbers: YO28762
First Submitted: October 23, 2015
First Posted: October 26, 2015
Results First Submitted: October 22, 2018
Results First Posted: January 3, 2019
Last Update Posted: June 25, 2019