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A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00545688
Recruitment Status : Completed
First Posted : October 17, 2007
Results First Posted : January 26, 2016
Last Update Posted : August 15, 2017
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: Herceptin
Drug: Docetaxel
Drug: Pertuzumab
Enrollment 417
Recruitment Details A total of 107, 107, 107, and 96 participants (total 417) were randomized to Arms Trastuzumab plus (+) Docetaxel (T+ D) , Trastuzumab+Pertuzumab+Docetaxel (T+Ptz+D), Trastuzumab+Pertuzumab (T+Ptz), and Pertuzumab+Docetaxel (Ptz+D), respectively and were included in intent-to-treat population (as randomized).
Pre-assignment Details 3 participants did not receive correct treatment, as randomized, and 1 (in Arm Trastuzumab + Docetaxel) did not receive any treatment. Safety population (as treated) included 107, 107, 108, and 94 participants in Arms ‘T+D’, ‘T+Ptz+D’, ‘T+Ptz’, and ‘Ptz+D’, respectively. Participant flow was available for “As Treated” participants.
Arm/Group Title Trastuzumab + Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab intravenous (IV) infusion at a loading dose of 8 milligrams per kilogram (mg/kg) on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 milligrams per square meter (mg/m^2) on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by 5-fluorouracil 600 mg/m^2 IV, epirubicin 90 mg/m^2 IV, and cyclophosphamide 600 mg/m^2 IV (FEC) on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Period Title: Neo-Adjuvant Treatment Period
Started 107 107 108 94
Completed 103 102 94 88
Not Completed 4 5 14 6
Reason Not Completed
Protocol Violation             1             2             1             1
Refused Treatment             1             1             4             1
Lost to Follow-up             1             0             0             0
Death             0             1             0             0
Disease Progression             0             1             7             2
Unknown Reason             1             0             0             0
Adverse Event             0             0             2             2
Period Title: Adjuvant Treatment Period
Started 103 102 94 88
Completed 98 94 90 74
Not Completed 5 8 4 14
Reason Not Completed
Disease Progression             3             3             0             7
Refused Treatment             1             1             1             5
Lost to Follow-up             1             0             1             0
Adverse Event             0             3             2             2
Unknown Reason             0             1             0             0
Period Title: Follow-Up Period
Started 98 102 98 87
Completed 77 83 78 60
Not Completed 21 19 20 27
Reason Not Completed
Death             4             2             2             6
Disease Progression             6             5             9             9
Refused Treatment             6             2             0             2
Lost to Follow-up             3             3             3             1
Unspecified Reason             2             5             6             8
Violation of Selection Criteria at Entry             0             2             0             1
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel Total
Hide Arm/Group Description

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Total of all reporting groups
Overall Number of Baseline Participants 107 107 107 96 417
Hide Baseline Analysis Population Description
Intent-To-Treat (ITT) Population included all randomized participants who received any amount of study medication. Analysis was performed according to initial randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 107 participants 107 participants 107 participants 96 participants 417 participants
50.9  (8.94) 49.6  (10.05) 49.7  (10.67) 48.9  (10.50) 49.8  (10.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 107 participants 107 participants 96 participants 417 participants
Female
107
 100.0%
107
 100.0%
107
 100.0%
96
 100.0%
417
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Participants Achieving Pathological Complete Response (pCR)
Hide Description pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders
Time Frame Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
29.0
(20.6 to 38.5)
45.8
(36.1 to 55.7)
16.8
(10.3 to 25.3)
24.0
(15.8 to 33.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab+Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0094
Comments Cochran-Mantel-Haenszel test stratified by breast cancer type (operable, locally advanced, or inflammatory) and estrogen and or progesterone positivity (either positive versus both negative).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response rates
Estimated Value 16.82
Confidence Interval (2-Sided) 95%
3.5 to 30.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab+Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0141
Comments P-value from Cochran-Mantel-Haenszel test, with Simes multiplicity adjustment.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0198
Comments Cochran-Mantel-Haenszel test stratified by breast cancer type (operable, locally advanced, or inflammatory) and estrogen and or progesterone positivity (either positive versus both negative).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response rates
Estimated Value -12.15
Confidence Interval (2-Sided) 95%
-23.8 to -0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0198
Comments P-value from Cochran-Mantel-Haenszel test, with Simes multiplicity adjustment.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Pertuzumab+Docetaxel, Pertuzumab+Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments Cochran-Mantel-Haenszel test stratified by breast cancer type (operable, locally advanced, or inflammatory) and estrogen and or progesterone positivity (either positive versus both negative).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response rates
Estimated Value -21.84
Confidence Interval (2-Sided) 95%
-35.1 to -8.5
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Pertuzumab+Docetaxel, Pertuzumab+Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0030
Comments P-value from Cochran-Mantel-Haenszel test, with Simes multiplicity adjustment.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Achieving pCR by Breast Cancer Type
Hide Description pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Based on the type of breast cancer participants were categorized as those with 1. Operable breast cancer, 2. Inflammatory breast cancer and 3. Locally advanced breast cancer. Participants with invalid/missing pCR assessments were defined as non-responders.
Time Frame Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number (n) equal (=) number of participants included in the specified type of breast cancer.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Operable Breast Cancer (n=64,65,65,60)
23.4
(13.8 to 35.7)
47.7
(35.1 to 60.5)
16.9
(8.8 to 28.3)
26.7
(16.1 to 39.7)
Inflammatory Breast Cancer (n=7,10,7,5)
14.3
(0.4 to 57.9)
40.0
(12.2 to 73.8)
28.6
(3.7 to 71.0)
40.0
(5.3 to 85.3)
Locally Advance Breast Cancer (36,32,35,31)
41.7
(25.5 to 59.2)
43.8
(26.4 to 62.3)
14.3
(4.8 to 30.3)
16.1
(5.5 to 33.7)
3.Primary Outcome
Title Percentage of Participants Achieving pCR by Hormone Receptor Status
Hide Description pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants were classified as Estrogen and/or Progesterone positive (+ve), Estrogen and/or Progesterone negative (-ve) or receptor status unknown. Participants with invalid/missing pCR assessments were defined as non-responders.
Time Frame Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. n = number of participants included in the specified hormone receptor status.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Estrogen and/or Progesterone +ve (n=50,50,51,46)
20.0
(10.0 to 33.7)
26.0
(14.6 to 40.3)
5.9
(1.2 to 16.2)
17.4
(7.8 to 31.4)
Estrogen and/or Progesterone -ve (n=57,57,55,50)
36.8
(24.4 to 50.7)
63.2
(49.3 to 75.6)
27.3
(16.1 to 41.0)
30.0
(17.9 to 44.6)
Receptor Status Unknown (0,0,1,0)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
0.0
(0.0 to 97.5)
NA [1] 
(NA to NA)
[1]
There were no participants in this category.
4.Primary Outcome
Title Percentage of Participants Achieving pCR by Lymph Node Status
Hide Description pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Lymph node status was defined as either negative lymph node at surgery or positive lymph node at surgery. Participants with invalid/missing pCR assessments were defined as non-responders.
Time Frame Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Measure Type: Number
Unit of Measure: percentage of participants
pCR achieved and Negative Lymph Nodes at Surgery 21.5 39.3 11.2 17.7
pCR achieved and Positive Lymph Nodes at Surgery 7.5 6.5 5.6 6.3
5.Primary Outcome
Title Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)
Hide Description pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders.
Time Frame Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Measure Type: Number
Unit of Measure: percentage of participants
pCR Achieved and No residual DCIS/LCIS at Surgery 16.8 36.4 9.3 17.7
pCR Achieved and Residual DCIS/LCIS at Surgery 12.1 9.3 7.5 6.3
6.Secondary Outcome
Title Percentage of Participants Achieving Best Primary Tumor Response (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Disease Progression [PD]) During Neo-Adjuvant Treatment by X-Ray/Mammography
Hide Description Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of ‘0’ is noted at a given cycle as compared to baseline measurement which is greater than (>)0 at screening or cycle 1 Day 1; PR: if measurement is at least a 30 percent (%) decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline.
Time Frame Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 71 58 61 47
Measure Type: Number
Unit of Measure: percentage of participants
CR 18.3 19.0 13.1 19.1
PR 49.3 46.6 36.1 46.8
SD 31.0 32.8 44.3 34.0
PD 1.4 1.7 6.6 0.0
7.Secondary Outcome
Title Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
Hide Description Tumor assessments were made based on the RECIST criteria - version 1.0 The overall response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of ‘0’ is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.
Time Frame Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 71 53 55 43
Measure Type: Number
Unit of Measure: percentage of participants
CR 18.3 18.9 12.7 18.6
PR 49.3 49.1 34.5 46.5
SD 31.0 30.2 45.5 34.9
PD 1.4 1.9 7.3 0.0
8.Secondary Outcome
Title Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
Hide Description Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of ‘0’ is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.
Time Frame Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 99 101 102 91
Measure Type: Number
Unit of Measure: percentage of participants
CR 23.2 30.7 16.7 20.9
PR 56.6 57.4 51.0 50.5
SD 20.2 11.9 30.4 28.6
PD 0.0 0.0 2.0 0.0
9.Secondary Outcome
Title Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
Hide Description Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of ‘0’ is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.
Time Frame Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 97 100 98 88
Measure Type: Number
Unit of Measure: percentage of participants
CR 21.6 25.0 11.2 15.9
PR 59.8 63.0 55.1 58.0
SD 17.5 12.0 31.6 26.1
PD 1.0 0.0 2.0 0.0
10.Secondary Outcome
Title Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography
Hide Description Clinical response was determined based on tumor measurements by sponsor in combination with tumor response assessment by investigator. Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of ‘0’ is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Overall response is derived based on the sum total of breast tumors and all nodes examined.
Time Frame Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome and n = number participants analyzed in the specified category.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 71 58 61 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Primary Breast Tumor (n=71,58,61,47)
67.6
(55.5 to 78.2)
65.5
(51.9 to 77.5)
49.2
(36.1 to 62.3)
66.0
(50.7 to 79.1)
Overall Response (n=71,53,55,43)
67.6
(55.5 to 78.2)
67.9
(53.7 to 80.1)
47.3
(33.7 to 61.2)
65.1
(49.1 to 79.0)
11.Secondary Outcome
Title Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination
Hide Description Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of ‘0’ is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Primary breast tumor clinical response is based on primary breast tumor assessment. Overall response is derived based on the sum total of breast tumors and all nodes examined.
Time Frame Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome and n = number participants analyzed in the specified category.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 99 101 102 91
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Primary Breast Tumor (n=99,101,102,91)
79.8
(70.5 to 87.2)
88.1
(80.2 to 93.7)
67.6
(57.7 to 76.6)
71.4
(61.0 to 80.4)
Overall Response (n=97,100,98,88)
81.4
(72.3 to 88.6)
88.0
(80.0 to 93.6)
66.3
(56.1 to 75.6)
73.9
(63.4 to 82.7)
12.Secondary Outcome
Title Time to Clinical Response During Neo-Adjuvant Treatment Period
Hide Description Time to clinical response was defined as the time from the date of first dose received to the date of assessment of clinical response. Time to Clinical response was determined by Kaplan-Meier estimates. Tumor assessments were made based on the RECIST criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment.
Time Frame Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 99 101 102 91
Median (80% Confidence Interval)
Unit of Measure: months
6.3
(6.0 to 7.0)
6.3
(4.0 to 7.0)
6.9
(6.0 to 9.0)
7.3
(6.0 to 9.0)
13.Secondary Outcome
Title Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period
Hide Description Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: PD: if lesion is at least a 20 % increased from measurements at baseline. Percentage of participants along with 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method were reported. Missing investigator assessments were considered as no progressive disease.
Time Frame Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a loading dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a loading dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a loading dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 3.4)
0.9
(0.0 to 5.1)
7.5
(3.3 to 14.2)
2.1
(0.3 to 7.3)
14.Secondary Outcome
Title Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned
Hide Description Breast Conserving Surgery (BCS) was defined as quadrantectomy, lumpectomy, no surgery, sentinel node biopsy, axillary surgical resection or other method of avoiding mastectomy.
Time Frame Surgery (Within 2 weeks after Cycle 4) Up to approximately 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 62 56 61 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.6
(12.9 to 35.0)
23.2
(13.0 to 36.4)
18.0
(9.4 to 30.0)
31.7
(20.3 to 45.0)
15.Secondary Outcome
Title Percentage of Participants Who Were Progression Free and Disease Free
Hide Description Disease-free survival (DFS) was defined as the time from first date of no disease to first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from the study without documented progression and for whom evaluations were made, were censored at date of last assessment when participant was known to be disease-free. Progression-free survival (PFS) was defined as time from date of randomization to first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from study without documented progression and for whom evaluations were made, were censored at date of last assessment when the participant was known to be free from progressive disease. Participants without post baseline assessments but known to be alive were censored at the time of randomization.
Time Frame Randomization up to a maximum of 329 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Measure Type: Number
Unit of Measure: percentage of participants
Progression Free 82.2 84.1 74.8 75.0
Disease Free 82.5 85.1 80.2 76.1
16.Secondary Outcome
Title Progression Free and Disease Free Survival
Hide Description DFS was defined as the time from the first date of no disease (date of surgery) to the first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. PFS was defined as the time from the date of randomization to the first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. DFS and PFS were determined using Kaplan-Meier estimates.
Time Frame Randomization up to a maximum of 329 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population; Analysis was performed according to initial randomization.
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Hide Arm/Group Description:

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Overall Number of Participants Analyzed 107 107 107 96
Median (80% Confidence Interval)
Unit of Measure: percentage of participants
PFS
NA [1] 
(NA to NA)
71.0
(71.0 to 76.0)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
DFS
NA [1] 
(NA to NA)
67.2
(67.0 to 72.0)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and corresponding 80% confidence interval were not achieved due to o the low number of events in this participant population, as expected.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab+Docetaxel
Comments PFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2983
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.34 to 1.40
Estimation Comments HR is based on Cox proportional hazard regression stratified by breast cancer type and hormone positivity.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab
Comments PFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4722
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.68 to 2.30
Estimation Comments HR is based on Cox proportional hazard regression stratified by breast cancer type and hormone positivity.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Pertuzumab+Docetaxel, Pertuzumab+Docetaxel
Comments PFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0268
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.05
Confidence Interval (2-Sided) 95%
1.07 to 3.93
Estimation Comments HR is based on Cox proportional hazard regression stratified by breast cancer type and hormone positivity.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab+Docetaxel
Comments DFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1805
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.28 to 1.27
Estimation Comments HR is based on Cox proportional hazard regression stratified by breast cancer type and hormone positivity.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Docetaxel, Trastuzumab+Pertuzumab
Comments DFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5901
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.42 to 1.64
Estimation Comments HR is based on Cox proportional hazard regression stratified by breast cancer type and hormone positivity.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Trastuzumab+Pertuzumab+Docetaxel, Pertuzumab+Docetaxel
Comments DFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0250
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.16
Confidence Interval (2-Sided) 95%
1.08 to 4.32
Estimation Comments HR is based on Cox proportional hazard regression stratified by breast cancer type and hormone positivity.
Time Frame Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
Adverse Event Reporting Description The safety population included all participants who received at least one dose of study medication and at least one safety assessment performed at baseline. Participants were assigned to treatment groups according to treatment actually received.
 
Arm/Group Title Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
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Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

All-Cause Mortality
Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/107 (19.63%)   22/107 (20.56%)   19/108 (17.59%)   21/94 (22.34%) 
Blood and lymphatic system disorders         
Febrile neutropenia * 1  10/107 (9.35%)  8/107 (7.48%)  4/108 (3.70%)  12/94 (12.77%) 
Neutropenia * 1  1/107 (0.93%)  6/107 (5.61%)  3/108 (2.78%)  6/94 (6.38%) 
Cardiac disorders         
Left ventricular dysfunction * 1  0/107 (0.00%)  3/107 (2.80%)  0/108 (0.00%)  0/94 (0.00%) 
Angina pectoris * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
Cardiac failure congestive * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Gastrointestinal disorders         
Diarrhoea * 1  2/107 (1.87%)  0/107 (0.00%)  0/108 (0.00%)  1/94 (1.06%) 
Abdominal strangulated hernia * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
Duodenal ulcer haemorrhage * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
General disorders         
Pyrexia * 1  1/107 (0.93%)  1/107 (0.93%)  2/108 (1.85%)  1/94 (1.06%) 
Imparied healing * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Hepatobiliary disorders         
Cholecystitis acute * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
Hepatitis fulminant * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
Immune system disorders         
Drug hypersensitivity * 1  0/107 (0.00%)  1/107 (0.93%)  1/108 (0.93%)  0/94 (0.00%) 
Infections and infestations         
Neutropenic infection * 1  1/107 (0.93%)  1/107 (0.93%)  1/108 (0.93%)  0/94 (0.00%) 
Appendicitis * 1  1/107 (0.93%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Pyelonephritis acute * 1  0/107 (0.00%)  2/107 (1.87%)  0/108 (0.00%)  0/94 (0.00%) 
Urinary tract infection * 1  1/107 (0.93%)  0/107 (0.00%)  0/108 (0.00%)  0/94 (0.00%) 
Wound infection * 1  2/107 (1.87%)  0/107 (0.00%)  0/108 (0.00%)  0/94 (0.00%) 
Breast abscess * 1  1/107 (0.93%)  0/107 (0.00%)  0/108 (0.00%)  0/94 (0.00%) 
Cellulitis * 1  0/107 (0.00%)  0/107 (0.00%)  0/108 (0.00%)  1/94 (1.06%) 
Device related infection * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
H1N1 influenza * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
Infection * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Neutropenic sepsis * 1  1/107 (0.93%)  0/107 (0.00%)  0/108 (0.00%)  0/94 (0.00%) 
Pneumonia * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Sepsis * 1  0/107 (0.00%)  0/107 (0.00%)  0/108 (0.00%)  1/94 (1.06%) 
Septic shock * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Staphylococcal sepsis * 1  0/107 (0.00%)  0/107 (0.00%)  0/108 (0.00%)  1/94 (1.06%) 
Injury, poisoning and procedural complications         
Femur fracture * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Upper limb fracture * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
Wound dehiscence * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Spinal pain * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Tumour haemorrhage * 1  1/107 (0.93%)  0/107 (0.00%)  0/108 (0.00%)  0/94 (0.00%) 
Nervous system disorders         
Dural arteriovenous fistula * 1  0/107 (0.00%)  0/107 (0.00%)  0/108 (0.00%)  1/94 (1.06%) 
Reproductive system and breast disorders         
Metrorrhagia * 1  1/107 (0.93%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Ovarian cyst ruptured * 1  0/107 (0.00%)  0/107 (0.00%)  0/108 (0.00%)  1/94 (1.06%) 
Ovarian disorder * 1  1/107 (0.93%)  0/107 (0.00%)  0/108 (0.00%)  0/94 (0.00%) 
Uterine haemorrhage * 1  0/107 (0.00%)  0/107 (0.00%)  0/108 (0.00%)  1/94 (1.06%) 
Respiratory, thoracic and mediastinal disorders         
Epistaxis * 1  1/107 (0.93%)  0/107 (0.00%)  0/108 (0.00%)  0/94 (0.00%) 
Skin and subcutaneous tissue disorders         
Rash papular * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Skin mass * 1  0/107 (0.00%)  0/107 (0.00%)  1/108 (0.93%)  0/94 (0.00%) 
Vascular disorders         
Venous insufficiency * 1  0/107 (0.00%)  1/107 (0.93%)  0/108 (0.00%)  0/94 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trastuzumab+Docetaxel Trastuzumab+Pertuzumab+Docetaxel Trastuzumab+Pertuzumab Pertuzumab+Docetaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   107/107 (100.00%)   105/107 (98.13%)   101/108 (93.52%)   94/94 (100.00%) 
Blood and lymphatic system disorders         
Neutropenia * 1  80/107 (74.77%)  64/107 (59.81%)  46/108 (42.59%)  67/94 (71.28%) 
Leukopenia * 1  24/107 (22.43%)  13/107 (12.15%)  13/108 (12.04%)  15/94 (15.96%) 
Anaemia * 1  9/107 (8.41%)  6/107 (5.61%)  11/108 (10.19%)  12/94 (12.77%) 
Cardiac disorders         
Palpitations * 1  2/107 (1.87%)  5/107 (4.67%)  7/108 (6.48%)  5/94 (5.32%) 
Left ventricular dysfunction * 1  2/107 (1.87%)  6/107 (5.61%)  2/108 (1.85%)  5/94 (5.32%) 
Eye disorders         
Lacrimation increased * 1  3/107 (2.80%)  8/107 (7.48%)  6/108 (5.56%)  6/94 (6.38%) 
Gastrointestinal disorders         
Nausea * 1  70/107 (65.42%)  71/107 (66.36%)  52/108 (48.15%)  61/94 (64.89%) 
Diarrhoea * 1  40/107 (37.38%)  55/107 (51.40%)  46/108 (42.59%)  52/94 (55.32%) 
Vomiting * 1  31/107 (28.97%)  39/107 (36.45%)  31/108 (28.70%)  37/94 (39.36%) 
Stomatitis * 1  12/107 (11.21%)  22/107 (20.56%)  21/108 (19.44%)  11/94 (11.70%) 
Abdominal pain upper * 1  8/107 (7.48%)  9/107 (8.41%)  12/108 (11.11%)  12/94 (12.77%) 
Constipation * 1  12/107 (11.21%)  14/107 (13.08%)  9/108 (8.33%)  6/94 (6.38%) 
Abdominal pain * 1  9/107 (8.41%)  11/107 (10.28%)  8/108 (7.41%)  10/94 (10.64%) 
Haemorrhoids * 1  5/107 (4.67%)  8/107 (7.48%)  8/108 (7.41%)  4/94 (4.26%) 
Dyspepsia * 1  6/107 (5.61%)  6/107 (5.61%)  6/108 (5.56%)  5/94 (5.32%) 
Abdominal distension * 1  1/107 (0.93%)  1/107 (0.93%)  2/108 (1.85%)  5/94 (5.32%) 
General disorders         
Fatigue * 1  35/107 (32.71%)  35/107 (32.71%)  34/108 (31.48%)  37/94 (39.36%) 
Mucosal inflammation * 1  28/107 (26.17%)  33/107 (30.84%)  18/108 (16.67%)  28/94 (29.79%) 
Asthenia * 1  22/107 (20.56%)  29/107 (27.10%)  19/108 (17.59%)  23/94 (24.47%) 
Pyrexia * 1  16/107 (14.95%)  25/107 (23.36%)  21/108 (19.44%)  14/94 (14.89%) 
Oedema peripheral * 1  12/107 (11.21%)  7/107 (6.54%)  18/108 (16.67%)  9/94 (9.57%) 
Chills * 1  8/107 (7.48%)  4/107 (3.74%)  10/108 (9.26%)  2/94 (2.13%) 
Chest pain * 1  4/107 (3.74%)  2/107 (1.87%)  4/108 (3.70%)  6/94 (6.38%) 
Pain * 1  2/107 (1.87%)  3/107 (2.80%)  3/108 (2.78%)  7/94 (7.45%) 
Oedema * 1  1/107 (0.93%)  0/107 (0.00%)  6/108 (5.56%)  4/94 (4.26%) 
General Disorder * 1  17/107 (15.89%)  16/107 (14.95%)  15/108 (13.89%)  26/94 (27.66%) 
Immune system disorders         
Drug hypersensitivity * 1  2/107 (1.87%)  6/107 (5.61%)  12/108 (11.11%)  6/94 (6.38%) 
Infections and infestations         
Upper respiratory tract infection * 1  12/107 (11.21%)  9/107 (8.41%)  11/108 (10.19%)  13/94 (13.83%) 
Nasopharyngitis * 1  12/107 (11.21%)  8/107 (7.48%)  7/108 (6.48%)  5/94 (5.32%) 
Pharyngitis * 1  8/107 (7.48%)  4/107 (3.74%)  4/108 (3.70%)  5/94 (5.32%) 
Urinary tract infection * 1  7/107 (6.54%)  4/107 (3.74%)  3/108 (2.78%)  6/94 (6.38%) 
Injury, poisoning and procedural complications         
Radiation skin injury * 1  21/107 (19.63%)  19/107 (17.76%)  22/108 (20.37%)  24/94 (25.53%) 
Infusion related reaction * 1  6/107 (5.61%)  7/107 (6.54%)  8/108 (7.41%)  8/94 (8.51%) 
Seroma * 1  6/107 (5.61%)  7/107 (6.54%)  4/108 (3.70%)  5/94 (5.32%) 
Procedural pain * 1  2/107 (1.87%)  3/107 (2.80%)  6/108 (5.56%)  2/94 (2.13%) 
Incision site pain * 1  1/107 (0.93%)  2/107 (1.87%)  3/108 (2.78%)  5/94 (5.32%) 
Investigations         
Alanine aminotransferase increased * 1  9/107 (8.41%)  2/107 (1.87%)  2/108 (1.85%)  5/94 (5.32%) 
Weight increased * 1  4/107 (3.74%)  2/107 (1.87%)  9/108 (8.33%)  1/94 (1.06%) 
Aspartate aminotransferase increased * 1  9/107 (8.41%)  0/107 (0.00%)  2/108 (1.85%)  2/94 (2.13%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  19/107 (17.76%)  18/107 (16.82%)  15/108 (13.89%)  23/94 (24.47%) 
Musculoskeletal and connective tissue disorders         
Myalgia * 1  24/107 (22.43%)  25/107 (23.36%)  29/108 (26.85%)  22/94 (23.40%) 
Arthralgia * 1  16/107 (14.95%)  18/107 (16.82%)  13/108 (12.04%)  19/94 (20.21%) 
Musculoskeletal pain * 1  13/107 (12.15%)  13/107 (12.15%)  5/108 (4.63%)  11/94 (11.70%) 
Bone pain * 1  13/107 (12.15%)  11/107 (10.28%)  7/108 (6.48%)  8/94 (8.51%) 
Back pain * 1  7/107 (6.54%)  7/107 (6.54%)  8/108 (7.41%)  11/94 (11.70%) 
Pain in extremity * 1  9/107 (8.41%)  7/107 (6.54%)  7/108 (6.48%)  6/94 (6.38%) 
Nervous system disorders         
Headache * 1  17/107 (15.89%)  14/107 (13.08%)  25/108 (23.15%)  22/94 (23.40%) 
Dysgeusia * 1  16/107 (14.95%)  16/107 (14.95%)  14/108 (12.96%)  10/94 (10.64%) 
Peripheral sensory neuropathy * 1  14/107 (13.08%)  10/107 (9.35%)  15/108 (13.89%)  14/94 (14.89%) 
Dizziness * 1  8/107 (7.48%)  6/107 (5.61%)  14/108 (12.96%)  8/94 (8.51%) 
Neuropathy peripheral * 1  10/107 (9.35%)  6/107 (5.61%)  4/108 (3.70%)  5/94 (5.32%) 
Paraesthesia * 1  7/107 (6.54%)  2/107 (1.87%)  3/108 (2.78%)  5/94 (5.32%) 
Psychiatric disorders         
Insomnia * 1  14/107 (13.08%)  13/107 (12.15%)  8/108 (7.41%)  14/94 (14.89%) 
Anxiety * 1  2/107 (1.87%)  3/107 (2.80%)  6/108 (5.56%)  0/94 (0.00%) 
Reproductive system and breast disorders         
Menstruation irregular * 1  7/107 (6.54%)  4/107 (3.74%)  10/108 (9.26%)  9/94 (9.57%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  11/107 (10.28%)  9/107 (8.41%)  19/108 (17.59%)  12/94 (12.77%) 
Epistaxis * 1  6/107 (5.61%)  11/107 (10.28%)  6/108 (5.56%)  6/94 (6.38%) 
Oropharyngeal pain * 1  7/107 (6.54%)  9/107 (8.41%)  2/108 (1.85%)  10/94 (10.64%) 
Dyspnoea * 1  5/107 (4.67%)  7/107 (6.54%)  7/108 (6.48%)  4/94 (4.26%) 
Skin and subcutaneous tissue disorders         
Alopecia * 1  75/107 (70.09%)  73/107 (68.22%)  59/108 (54.63%)  65/94 (69.15%) 
Rash * 1  26/107 (24.30%)  30/107 (28.04%)  22/108 (20.37%)  30/94 (31.91%) 
Nail disorder * 1  17/107 (15.89%)  13/107 (12.15%)  16/108 (14.81%)  13/94 (13.83%) 
Pruritus * 1  8/107 (7.48%)  5/107 (4.67%)  10/108 (9.26%)  8/94 (8.51%) 
Erythema * 1  5/107 (4.67%)  6/107 (5.61%)  7/108 (6.48%)  11/94 (11.70%) 
Skin hyperpigmentation * 1  5/107 (4.67%)  7/107 (6.54%)  2/108 (1.85%)  6/94 (6.38%) 
Urticaria * 1  1/107 (0.93%)  6/107 (5.61%)  4/108 (3.70%)  7/94 (7.45%) 
Acne * 1  3/107 (2.80%)  7/107 (6.54%)  2/108 (1.85%)  4/94 (4.26%) 
Dry skin * 1  7/107 (6.54%)  2/107 (1.87%)  3/108 (2.78%)  2/94 (2.13%) 
Vascular disorders         
Hot flush * 1  11/107 (10.28%)  12/107 (11.21%)  8/108 (7.41%)  7/94 (7.45%) 
Lymphoedema * 1  4/107 (3.74%)  6/107 (5.61%)  12/108 (11.11%)  5/94 (5.32%) 
Flushing * 1  6/107 (5.61%)  5/107 (4.67%)  5/108 (4.63%)  5/94 (5.32%) 
Hypertension * 1  5/107 (4.67%)  6/107 (5.61%)  4/108 (3.70%)  3/94 (3.19%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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 after the first publication or presentation that involves the overall study. 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: Hoffmannb-LaRoche
Phone: 1-800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00545688     History of Changes
Other Study ID Numbers: WO20697
First Submitted: October 16, 2007
First Posted: October 17, 2007
Results First Submitted: December 16, 2015
Results First Posted: January 26, 2016
Last Update Posted: August 15, 2017