Clinical Trial Results:
A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients with Operable HER2-Positive Primary Breast Cancer
Summary
|
|
EudraCT number |
2010-022902-41 |
Trial protocol |
GB HU CZ ES FR IE SE DK SI NL BE SK AT IT BG |
Global end of trial date |
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
22 Dec 2017
|
First version publication date |
22 Dec 2017
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
BO25126
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01358877 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Genentech protocol code: TOC4939g, Breast International Group: BIG 4-11 | ||
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
|
||
Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
|
||
Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Interim
|
||
Date of interim/final analysis |
19 Dec 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
19 Dec 2016
|
||
Global end of trial reached? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The primary objective of this study was to compare invasive disease-free survival (IDFS) (excluding second non breast cancers) in participants with human epidermal growth receptor 2 (HER2)-positive early breast cancer randomized to chemotherapy plus 1 year of trastuzumab plus placebo, or chemotherapy plus 1 year of trastuzumab plus pertuzumab.
|
||
Protection of trial subjects |
The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) according to the regulations and procedures described in the protocol. Approval from the Institutional Review Board (IRB)/Ethics Committees (ECs) was obtained before study start. The sponsor also obtained approval from the relevant regulatory authorities prior to starting the study.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Nov 2011
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
10 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Argentina: 3
|
||
Country: Number of subjects enrolled |
Australia: 109
|
||
Country: Number of subjects enrolled |
Austria: 52
|
||
Country: Number of subjects enrolled |
Belgium: 131
|
||
Country: Number of subjects enrolled |
Bulgaria: 21
|
||
Country: Number of subjects enrolled |
Canada: 110
|
||
Country: Number of subjects enrolled |
Chile: 14
|
||
Country: Number of subjects enrolled |
China: 372
|
||
Country: Number of subjects enrolled |
Colombia: 13
|
||
Country: Number of subjects enrolled |
Croatia: 15
|
||
Country: Number of subjects enrolled |
Czech Republic: 26
|
||
Country: Number of subjects enrolled |
Denmark: 87
|
||
Country: Number of subjects enrolled |
El Salvador: 7
|
||
Country: Number of subjects enrolled |
France: 544
|
||
Country: Number of subjects enrolled |
Germany: 460
|
||
Country: Number of subjects enrolled |
Guatemala: 12
|
||
Country: Number of subjects enrolled |
Hong Kong: 16
|
||
Country: Number of subjects enrolled |
Hungary: 63
|
||
Country: Number of subjects enrolled |
Ireland: 43
|
||
Country: Number of subjects enrolled |
Israel: 39
|
||
Country: Number of subjects enrolled |
Italy: 255
|
||
Country: Number of subjects enrolled |
Japan: 302
|
||
Country: Number of subjects enrolled |
Mexico: 35
|
||
Country: Number of subjects enrolled |
Netherlands: 24
|
||
Country: Number of subjects enrolled |
New Zealand: 19
|
||
Country: Number of subjects enrolled |
Panama: 15
|
||
Country: Number of subjects enrolled |
Peru: 25
|
||
Country: Number of subjects enrolled |
Philippines: 36
|
||
Country: Number of subjects enrolled |
Poland: 110
|
||
Country: Number of subjects enrolled |
Romania: 25
|
||
Country: Number of subjects enrolled |
Russian Federation: 58
|
||
Country: Number of subjects enrolled |
Slovenia: 9
|
||
Country: Number of subjects enrolled |
South Africa: 21
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 136
|
||
Country: Number of subjects enrolled |
Spain: 343
|
||
Country: Number of subjects enrolled |
Sweden: 72
|
||
Country: Number of subjects enrolled |
Switzerland: 50
|
||
Country: Number of subjects enrolled |
Taiwan: 170
|
||
Country: Number of subjects enrolled |
Thailand: 75
|
||
Country: Number of subjects enrolled |
Ukraine: 73
|
||
Country: Number of subjects enrolled |
United Kingdom: 224
|
||
Country: Number of subjects enrolled |
United States: 590
|
||
Worldwide total number of subjects |
4804
|
||
EEA total number of subjects |
2504
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
4196
|
||
From 65 to 84 years |
605
|
||
85 years and over |
3
|
|
||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
The analysis included data up to a clinical data cut-off date of 19 December 2016. | |||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
Arm title
|
Pertuzumab + Trastuzumab + Chemotherapy | |||||||||||||||||||||||||||
Arm description |
Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Pertuzumab
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
RO4368451
|
|||||||||||||||||||||||||||
Other name |
Perjeta®, rhuMAb 2C4
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
|||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Pertuzumab will be administered as per the schedule specified in the arm description.
|
|||||||||||||||||||||||||||
Arm title
|
Placebo + Trastuzumab + Chemotherapy | |||||||||||||||||||||||||||
Arm description |
Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 milligrams per kilogram [mg/kg] loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 milligrams [mg]). | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
|||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Placebo matched to pertuzumab will be administered as per the schedule specified in the arm.
|
|||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pertuzumab + Trastuzumab + Chemotherapy
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg). | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + Trastuzumab + Chemotherapy
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 milligrams per kilogram [mg/kg] loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 milligrams [mg]). | ||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Pertuzumab + Trastuzumab + Chemotherapy
|
||
Reporting group description |
Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg). | ||
Reporting group title |
Placebo + Trastuzumab + Chemotherapy
|
||
Reporting group description |
Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 milligrams per kilogram [mg/kg] loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 milligrams [mg]). | ||
Subject analysis set title |
Pertuzumab + Trastuzumab + Chemotherapy
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
|
||
Subject analysis set title |
Placebo + Trastuzumab + Chemotherapy
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
|
||
Subject analysis set title |
Pertuzumab + Trastuzumab + Chemotherapy
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
|
||
Subject analysis set title |
Placebo + Trastuzumab + Chemotherapy
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg).
|
|
|||||||||||||
End point title |
Percentage of Participants With IDFS Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Percentage of participants with IDFS events (excluding SPNBC) is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (that is [i.e.], an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event. Intent-to-treat (ITT) population included all randomized participants regardless of treatment received.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Randomization to the first occurrence of IDFS event (excluding SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization. Hazard ratios were estimated by Cox regression.
|
||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||
Number of subjects included in analysis |
4804
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0446 [1] | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.81
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.66 | ||||||||||||
upper limit |
1 | ||||||||||||
Notes [1] - Statistical significance was controlled at a two-sided alpha level of 0.05. |
|
|||||||||||||
End point title |
Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [2] | ||||||||||||
End point description |
Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (excluding SPNBC) at Year 3 is reported. IDFS event the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including DCIS and LCIS) and non-melanoma skin cancer were excluded as an event. ITT population. Number of subjects analysed = participants remaining at risk for IDFS event (excluding SPNBC) at Year 3.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
3 years
|
||||||||||||
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary outcome measure was analyzed for a relative treatment difference using the hazard ratio and log-rank test. Kaplan-Meier 3-year estimates of the primary outcome measure are only presented as additional descriptive summary statistics. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Percentage of participants with IDFS events (including SPNBC) is reported. IDFS-SPNBC event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). ITT population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomization to the first occurrence of IDFS event (including SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization. Hazard ratios were estimated by Cox regression.
|
||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||
Number of subjects included in analysis |
4804
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.043 [3] | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.82
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.68 | ||||||||||||
upper limit |
0.99 | ||||||||||||
Notes [3] - Statistical significance was controlled at a two-sided alpha level of 0.05. |
|
|||||||||||||
End point title |
Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (including SPNBC) at Year 3 is reported. IDFS-SPNBC event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). ITT population. Number of subjects analysed = participants remaining at risk for IDFS event (including SPNBC) at Year 3.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
3 years
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Percentage of participants with DFS event is reported. DFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS. ITT population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomization to the first occurrence of DFS event (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization. Hazard ratios were estimated by Cox regression.
|
||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||
Number of subjects included in analysis |
4804
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0327 [4] | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.81
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.67 | ||||||||||||
upper limit |
0.98 | ||||||||||||
Notes [4] - Statistical significance was controlled at a two-sided alpha level of 0.05. |
|
|||||||||||||
End point title |
Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Kaplan-Meier estimate of the percentage of participants who were DFS event-free at Year 3 is reported. DFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS. ITT population. Number of subjects analysed = participants remaining at risk for DFS event at Year 3.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
3 years
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants Who Died | ||||||||||||
End point description |
Percentage of participants who died due to any cause is reported. ITT population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomization until death due to any cause (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization. Hazard ratios were estimated by Cox regression.
|
||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||
Number of subjects included in analysis |
4804
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.4673 [5] | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.89
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.66 | ||||||||||||
upper limit |
1.21 | ||||||||||||
Notes [5] - Statistical significance was controlled at a two-sided alpha level of 0.05. |
|
|||||||||||||
End point title |
Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3 | ||||||||||||
End point description |
The Kaplan-Meier approach was used to estimate the percentage of participants who were alive at 3 years. ITT population. Number of subjects analysed = participants remaining at risk for death at Year 3.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
3 years
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Percentage of participants with RFI event is reported. RFI event was defined as local, regional or distant breast cancer recurrence. ITT population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomization until local, regional or distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization. Hazard ratio were estimated by Cox regression.
|
||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||
Number of subjects included in analysis |
4804
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.043 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.79
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.63 | ||||||||||||
upper limit |
0.99 |
|
|||||||||||||
End point title |
Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Kaplan-Meier estimate of the percentage of participants who were RFI event-free at Year 3 is reported. RFI event was defined local, regional or distant breast cancer recurrence. ITT population. Number of subjects analysed = participants remaining at risk for RFI event at Year 3.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
3 years
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Percentage of participants with DRFI event is reported. DRFI event was defined as distant breast cancer recurrence. ITT population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomization until distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Analysis was performed using stratified log-rank test, which included nodal status, protocol version, central hormone receptor status, and adjuvant chemotherapy regimen as stratification factors in the randomization. Hazard ratio were estimated by Cox regression.
|
||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||
Number of subjects included in analysis |
4804
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.1007 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.82
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.64 | ||||||||||||
upper limit |
1.04 |
|
|||||||||||||
End point title |
Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings | ||||||||||||
End point description |
Kaplan-Meier estimate of the percentage of participants who were DRFI event-free at Year 3 is reported. DRFI event was defined as distant breast cancer recurrence. ITT population. Number of subjects analysed = participants remaining at risk for DRFI event at Year 3.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
3 years
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Percentage of Participants With Primary Cardiac Event | |||||||||||||||||||||
End point description |
Primary cardiac event was defined as either: Heart Failure (New York Heart Association [NYHA] Class III or IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction (EF) points from baseline and to below 50 percent (%); or cardiac death. Cardiac death was defined as either definite cardiac death: due to heart failure, myocardial infarction, or documented primary arrhythmia; or probable cardiac death: sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology. Safety population included participants who received any amount of study medication (chemotherapy, pertuzumab/placebo, or trastuzumab), according to the treatment actually received.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | |||||||||||||||||||||
Statistical analysis description |
The difference in percentage of participants with a primary cardiac event between the pertuzumab and placebo arms. The 95% confidence interval (CI) was estimated using Hauck-Anderson correction.
|
|||||||||||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
|||||||||||||||||||||
Number of subjects included in analysis |
4769
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Treatment Difference | |||||||||||||||||||||
Point estimate |
0.4
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
0 | |||||||||||||||||||||
upper limit |
0.8 |
|
|||||||||||||
End point title |
Percentage of Participants With Secondary Cardiac Event | ||||||||||||
End point description |
Secondary cardiac event was defined as asymptomatic or mildly symptomatic (NYHA Class II) significant drop in LVEF (defined as an absolute decrease of at least 10 EF points from baseline and to below 50%), confirmed by a second LVEF assessment within approximately three weeks of the first significant LVEF assessment or confirmed by the Cardiac Advisory Board (CAB). Safety population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
95% CI was estimated using Hauck-Anderson correction.
|
||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||
Number of subjects included in analysis |
4769
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Treatment Difference | ||||||||||||
Point estimate |
-0.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1 | ||||||||||||
upper limit |
0.9 |
|
|||||||||||||||||||
End point title |
Change From Baseline in LVEF to Worst Post-Baseline Value | ||||||||||||||||||
End point description |
LVEF is the fraction of blood (in percent) pumped out of the heart’s left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. Baseline LVEF value and the maximum absolute decrease (worst value) in LVEF measurement from baseline were reported. LVEF was measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan. Safety population. "Number of subjects analysed"=participants evaluable for this endpoint. Here, n=participants evaluable for this endpoint at specified timepoint.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||
Statistical analysis description |
95% CI was estimated using Hauck-Anderson correction.
|
||||||||||||||||||
Comparison groups |
Pertuzumab + Trastuzumab + Chemotherapy v Placebo + Trastuzumab + Chemotherapy
|
||||||||||||||||||
Number of subjects included in analysis |
4764
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
Method |
|||||||||||||||||||
Parameter type |
Treatment Difference | ||||||||||||||||||
Point estimate |
0.1
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-0.3 | ||||||||||||||||||
upper limit |
0.5 |
|
||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score | |||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess overall quality of life(QOL)in cancer participants. First 28 questions used 4-point scale(1=not at all,2=a little,3=quite a bit,4=very much)for evaluating 5 functional scales(physical, role, social, cognitive, emotional),8 symptom scales(diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting[N/V], constipation, pain) and a single item (financial difficulties). Last 2 questions represented participant’s assessment of overall health and quality of life, used 7-point scale(1=very poor to 7=excellent). Global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better GHS/QOL. Negative change from Baseline values indicated deterioration in QOL or functioning. ITT population. "Number of subjects analysed"=participants evaluable for this endpoint. n= participants responding to this scale where it is considered complete as defined by EORTC QLQ-C30 scoring manual.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; end of treatment (EOT, 28 days after the last dose, up to Week 56); Follow-up (FU) Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant’s assessment of overall health and quality of life, coded on 7-point scale(1=very poor to 7=excellent). EORTC QLQ-C30 functioning scores were linearly transformed on a scale of 0 to 100, with a high score indicating better functioning/support. Negative change from Baseline values indicated deterioration in functioning. ITT population. "Number of subjects analysed"=participants evaluable for this endpoint. n= participants responding to this scale where it is considered complete as defined by EORTC QLQ-C30 scoring manual.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess overall QOL in cancer participants. First 28 questions used 4-point scale(1=not at all,2=a little,3=quite a bit,4=very much)for evaluating 5 functional scales (physical,role,social,cognitive,emotional), 8 symptom scales(diarrhea,fatigue,dyspnea,appetite loss,insomnia,nausea and vomiting[N/V],constipation,pain)and a single item(financial difficulties). Last 2 questions represented participant’s assessment of overall health and QOL, coded on 7-point scale(1=very poor to 7=excellent). EORTC QLQ-C30 disease/treatment-related symptom scores were linearly transformed on scale of 0 to 100, with high score indicating higher level of symptoms. Negative change from Baseline values indicated improvement in symptoms. ITT population. "Number of subjects analysed"=participants evaluable for this endpoint. n= participants responding to this scale where it is considered complete as defined by EORTC QLQ-C30 scoring manual.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores | |||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess overall QOL in cancer participants. First 28 questions used 4-point scale(1=not at all,2=a little,3=quite a bit,4=very much)for evaluating 5 functional scales (physical,role,social,cognitive,emotional), 8 symptom scales(diarrhea fatigue,dyspnea,appetite loss,insomnia,N/V,constipation,pain)and a single item(financial difficulties). Last 2 questions represented participant’s assessment of overall health and quality of life, coded on 7-point scale(1=very poor to 7=excellent). Financial difficulties scores were linearly transformed on a scale of 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicated improvement in financial difficulties. ITT population."Number of subjects analysed"=participants evaluable for this endpoint. n= participants responding to this scale where it is considered complete as defined by EORTC QLQ-C30 scoring manual.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. ITT population. "Number of subjects analysed"=participants evaluable for this endpoint. Here, n=participants evaluable for this endpoint at specified timepoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for symptom scale indicated high level of symptomatology/problems/greater degree of symptoms. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. ITT population. "Number of subjects analysed"=participants evaluable for this endpoint. Here, n=participants evaluable for this endpoint at specified timepoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in mobility domain was reported: I have no problems in walking about; I have some problems in walking about; and I am confined to bed. Response percentages may not add up to 100% due to data rounding. ITT population. Here, n=participants evaluable for this endpoint at specified timepoint.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in self-care domain was reported: I have no problems with self-care; I have some problems washing or dressing myself; and I am unable to wash or dress myself. Response percentages may not add up to 100% due to data rounding. ITT population. Here, n=participants evaluable for this endpoint at specified timepoint.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in usual activities domain was reported: I have no problems with performing my usual activities; I have some problems with performing my usual activities; and I am unable to perform my usual activities. Response percentages may not add up to 100% due to data rounding. ITT population. Here, n=participants evaluable for this endpoint at specified timepoint.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in pain/discomfort domain was reported: I have no pain or discomfort; I have moderate pain or discomfort; and I have extreme pain or discomfort. Response percentages may not add up to 100% due to data rounding. ITT population. Here, n=participants evaluable for this endpoint at specified timepoint.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in anxiety/depression domain was reported: I am not anxious or depressed; I am moderately anxious or depressed; and I am extremely anxious or depressed. Response percentages may not add up to 100% due to data rounding. ITT population. Here, n=participants evaluable for this endpoint at specified timepoint.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Trough Serum Concentration (Cmin) of Pertuzumab | ||||||||||||||
End point description |
Pharmacokinetic (PK) evaluable participants were defined as those who received at least one active pertuzumab and/or trastuzumab treatment and had at least one PK sample collected. Here, n=participants evaluable for this endpoint at specified timepoint.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Cycles 1, 10 and 15 (Cycle length=21 days)
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Cmin of Trastuzumab | |||||||||||||||||||||
End point description |
PK evaluable participants. Here, n=participants evaluable for this endpoint at specified timepoint.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Cycles 1, 10 and 15 (Cycle length=21 days)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Peak Serum Concentration (Cmax) of Pertuzumab | ||||||||||||||
End point description |
PK evaluable participants. Here, n=participants evaluable for this endpoint at specified timepoint.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Cycles 1, 10 and 15 (Cycle length=21 days)
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Cmax of Trastuzumab | |||||||||||||||||||||
End point description |
PK evaluable participants. Here, n=participants evaluable for this endpoint at specified timepoint.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Cycles 1, 10 and 15 (Cycle length=21 days)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Randomization until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety population. 38 participants randomized to pertuzumab arm received study treatment but did not receive pertuzumab and were included in the placebo arm for safety analyses. 24 participants randomized to placebo arm received at least 1 dose of pertuzumab and were included in pertuzumab arm for safety analyses.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pertuzumab + Trastuzumab + Chemotherapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + Trastuzumab + Chemotherapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received placebo matched to pertuzumab IV Q3W and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 mg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
20 Nov 2012 |
This amendment was made mainly to adjust for a higher than expected rate of recruitment of node-negative participants. The trial sample size was increased from N=3806 to N=4800 and node-negative participants were no longer permitted to enroll. The recruitment period was adjusted (from 27 to 25 months) and a clause was included to ensure that the primary analysis did not take place until at least 30 months after the last participant enrolled. Additional protocol revisions included following: - The time from randomization to first treatment was increased from 7 weeks to 8 weeks to allow participants more time to enter study. - The number of centers was reduced from 700 to 600. - The number of cycles of 5 fluorouracil, epirubicin and cyclophosphamide (FEC)/5-fluorouracil, doxorubicin and cyclophosphamide (FAC) was made more flexible (3 or 4) to more closely reflect local practice. - Reporting of non-breast second primary malignancies was added, in line with protocol-specified endpoints. - The minimum observation period after administration of pertuzumab was adjusted to align with the current pertuzumab label. - The order of administration of docetaxel, carboplatin and trastuzumab (TCH) was updated in line with current practice, in addition to clarifying the dose and time period of administration. - A range of clarifications were added including to the eligibility criteria (examples of concurrent serious diseases added), the requirements for participants undergoing sentinel lymph node biopsies, the reporting of concomitant medications and prior treatments for breast cancer, the information to be collected at the time of partial withdrawal from the study, and to the timing of assessments and sample collection. |
||
03 Dec 2013 |
This amendment consisted mainly of clarifications, corrections of minor inconsistencies and minor adjustments, as follows: - A 3-day window for the last dose of targeted therapy was added at the end of 52 weeks. - The investigational medicinal product (IMP) terminology was clarified to refer specifically to pertuzumab (‘targeted treatment’ referred to pertuzumab + trastuzumab; ‘study drugs’ referred to pertuzumab + trastuzumab + chemotherapy). - Due to multiple queries from sites, the language associated with the investigators’ choice of adjuvant chemotherapy was revised, and information on excluded anti-cancer agents was added. - Follow-up of adverse events was clarified (until resolution or end of study); also the assessment schedules for participants according to treatments received. Footnotes to the schedule of assessment tables were also added or revised, for example relating to the requirements for yearly mammograms. - Mentions of optional cores from the original tumor block for non-heritable factors were removed. |
||
02 Feb 2015 |
This amendment was made primarily to include details of enhanced measures for reporting of pregnancies that occur during study treatment or within 6 months after completion of pertuzumab treatment.
In addition, the following changes were made: - The washout period for trastuzumab was increased to 7 months based on updated half-life data for trastuzumab. - Related warnings (pregnancy exclusion and cardiac toxicity risk) were revised based on the updated trastuzumab washout period. - Endocrine therapy recommendations were revised (to allow endocrine therapy administration as per local practice). - An additional plasma sample at disease recurrence was added. - Various clarifications were made (to sample collection, definitions and reporting requirements). |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |