Trial Outcomes & Findings for A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer. (NCT NCT00545688)
NCT ID: NCT00545688
Last Updated: 2017-08-15
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
417 participants
Primary outcome timeframe
Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Results posted on
2017-08-15
Participant Flow
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).
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.
Participant milestones
| Measure |
Trastuzumab + Docetaxel
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.
|
Trastuzumab+Pertuzumab+Docetaxel
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.
|
Trastuzumab+Pertuzumab
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.
|
Pertuzumab+Docetaxel
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.
|
|---|---|---|---|---|
|
Neo-Adjuvant Treatment Period
STARTED
|
107
|
107
|
108
|
94
|
|
Neo-Adjuvant Treatment Period
COMPLETED
|
103
|
102
|
94
|
88
|
|
Neo-Adjuvant Treatment Period
NOT COMPLETED
|
4
|
5
|
14
|
6
|
|
Adjuvant Treatment Period
STARTED
|
103
|
102
|
94
|
88
|
|
Adjuvant Treatment Period
COMPLETED
|
98
|
94
|
90
|
74
|
|
Adjuvant Treatment Period
NOT COMPLETED
|
5
|
8
|
4
|
14
|
|
Follow-Up Period
STARTED
|
98
|
102
|
98
|
87
|
|
Follow-Up Period
COMPLETED
|
77
|
83
|
78
|
60
|
|
Follow-Up Period
NOT COMPLETED
|
21
|
19
|
20
|
27
|
Reasons for withdrawal
| Measure |
Trastuzumab + Docetaxel
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.
|
Trastuzumab+Pertuzumab+Docetaxel
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.
|
Trastuzumab+Pertuzumab
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.
|
Pertuzumab+Docetaxel
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.
|
|---|---|---|---|---|
|
Neo-Adjuvant Treatment Period
Protocol Violation
|
1
|
2
|
1
|
1
|
|
Neo-Adjuvant Treatment Period
Refused Treatment
|
1
|
1
|
4
|
1
|
|
Neo-Adjuvant Treatment Period
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Neo-Adjuvant Treatment Period
Death
|
0
|
1
|
0
|
0
|
|
Neo-Adjuvant Treatment Period
Disease Progression
|
0
|
1
|
7
|
2
|
|
Neo-Adjuvant Treatment Period
Unknown Reason
|
1
|
0
|
0
|
0
|
|
Neo-Adjuvant Treatment Period
Adverse Event
|
0
|
0
|
2
|
2
|
|
Adjuvant Treatment Period
Disease Progression
|
3
|
3
|
0
|
7
|
|
Adjuvant Treatment Period
Refused Treatment
|
1
|
1
|
1
|
5
|
|
Adjuvant Treatment Period
Lost to Follow-up
|
1
|
0
|
1
|
0
|
|
Adjuvant Treatment Period
Adverse Event
|
0
|
3
|
2
|
2
|
|
Adjuvant Treatment Period
Unknown Reason
|
0
|
1
|
0
|
0
|
|
Follow-Up Period
Death
|
4
|
2
|
2
|
6
|
|
Follow-Up Period
Disease Progression
|
6
|
5
|
9
|
9
|
|
Follow-Up Period
Refused Treatment
|
6
|
2
|
0
|
2
|
|
Follow-Up Period
Lost to Follow-up
|
3
|
3
|
3
|
1
|
|
Follow-Up Period
Unspecified Reason
|
2
|
5
|
6
|
8
|
|
Follow-Up Period
Violation of Selection Criteria at Entry
|
0
|
2
|
0
|
1
|
Baseline Characteristics
A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer.
Baseline characteristics by cohort
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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
n=417 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
50.9 years
STANDARD_DEVIATION 8.94 • n=5 Participants
|
49.6 years
STANDARD_DEVIATION 10.05 • n=7 Participants
|
49.7 years
STANDARD_DEVIATION 10.67 • n=5 Participants
|
48.9 years
STANDARD_DEVIATION 10.50 • n=4 Participants
|
49.8 years
STANDARD_DEVIATION 10.04 • n=21 Participants
|
|
Sex: Female, Male
Female
|
107 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
96 Participants
n=4 Participants
|
417 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)Population: ITT Population; Analysis was performed according to initial randomization.
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
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Pathological Complete Response (pCR)
|
29.0 percentage of participants
Interval 20.6 to 38.5
|
45.8 percentage of participants
Interval 36.1 to 55.7
|
16.8 percentage of participants
Interval 10.3 to 25.3
|
24.0 percentage of participants
Interval 15.8 to 33.7
|
PRIMARY outcome
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)Population: ITT Population; Analysis was performed according to initial randomization. Number (n) equal (=) number of participants included in the specified type of breast cancer.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving pCR by Breast Cancer Type
Operable Breast Cancer (n=64,65,65,60)
|
23.4 percentage of participants
Interval 13.8 to 35.7
|
47.7 percentage of participants
Interval 35.1 to 60.5
|
16.9 percentage of participants
Interval 8.8 to 28.3
|
26.7 percentage of participants
Interval 16.1 to 39.7
|
|
Percentage of Participants Achieving pCR by Breast Cancer Type
Inflammatory Breast Cancer (n=7,10,7,5)
|
14.3 percentage of participants
Interval 0.4 to 57.9
|
40.0 percentage of participants
Interval 12.2 to 73.8
|
28.6 percentage of participants
Interval 3.7 to 71.0
|
40.0 percentage of participants
Interval 5.3 to 85.3
|
|
Percentage of Participants Achieving pCR by Breast Cancer Type
Locally Advance Breast Cancer (36,32,35,31)
|
41.7 percentage of participants
Interval 25.5 to 59.2
|
43.8 percentage of participants
Interval 26.4 to 62.3
|
14.3 percentage of participants
Interval 4.8 to 30.3
|
16.1 percentage of participants
Interval 5.5 to 33.7
|
PRIMARY outcome
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)Population: ITT Population; Analysis was performed according to initial randomization. n = number of participants included in the specified hormone receptor status.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving pCR by Hormone Receptor Status
Estrogen and/or Progesterone +ve (n=50,50,51,46)
|
20.0 percentage of participants
Interval 10.0 to 33.7
|
26.0 percentage of participants
Interval 14.6 to 40.3
|
5.9 percentage of participants
Interval 1.2 to 16.2
|
17.4 percentage of participants
Interval 7.8 to 31.4
|
|
Percentage of Participants Achieving pCR by Hormone Receptor Status
Estrogen and/or Progesterone -ve (n=57,57,55,50)
|
36.8 percentage of participants
Interval 24.4 to 50.7
|
63.2 percentage of participants
Interval 49.3 to 75.6
|
27.3 percentage of participants
Interval 16.1 to 41.0
|
30.0 percentage of participants
Interval 17.9 to 44.6
|
|
Percentage of Participants Achieving pCR by Hormone Receptor Status
Receptor Status Unknown (0,0,1,0)
|
NA percentage of participants
There were no participants in this category.
|
NA percentage of participants
There were no participants in this category.
|
0.0 percentage of participants
Interval 0.0 to 97.5
|
NA percentage of participants
There were no participants in this category.
|
PRIMARY outcome
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)Population: ITT Population; Analysis was performed according to initial randomization.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving pCR by Lymph Node Status
pCR achieved and Negative Lymph Nodes at Surgery
|
21.5 percentage of participants
|
39.3 percentage of participants
|
11.2 percentage of participants
|
17.7 percentage of participants
|
|
Percentage of Participants Achieving pCR by Lymph Node Status
pCR achieved and Positive Lymph Nodes at Surgery
|
7.5 percentage of participants
|
6.5 percentage of participants
|
5.6 percentage of participants
|
6.3 percentage of participants
|
PRIMARY outcome
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)Population: ITT Population; Analysis was performed according to initial randomization.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)
pCR Achieved and No residual DCIS/LCIS at Surgery
|
16.8 percentage of participants
|
36.4 percentage of participants
|
9.3 percentage of participants
|
17.7 percentage of participants
|
|
Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)
pCR Achieved and Residual DCIS/LCIS at Surgery
|
12.1 percentage of participants
|
9.3 percentage of participants
|
7.5 percentage of participants
|
6.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=71 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=58 Participants
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.
|
Trastuzumab+Pertuzumab
n=61 Participants
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.
|
Pertuzumab+Docetaxel
n=47 Participants
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.
|
|---|---|---|---|---|
|
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
CR
|
18.3 percentage of participants
|
19.0 percentage of participants
|
13.1 percentage of participants
|
19.1 percentage of participants
|
|
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
PD
|
1.4 percentage of participants
|
1.7 percentage of participants
|
6.6 percentage of participants
|
0.0 percentage of participants
|
|
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
PR
|
49.3 percentage of participants
|
46.6 percentage of participants
|
36.1 percentage of participants
|
46.8 percentage of participants
|
|
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
SD
|
31.0 percentage of participants
|
32.8 percentage of participants
|
44.3 percentage of participants
|
34.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=71 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=53 Participants
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.
|
Trastuzumab+Pertuzumab
n=55 Participants
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.
|
Pertuzumab+Docetaxel
n=43 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
CR
|
18.3 percentage of participants
|
18.9 percentage of participants
|
12.7 percentage of participants
|
18.6 percentage of participants
|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
PR
|
49.3 percentage of participants
|
49.1 percentage of participants
|
34.5 percentage of participants
|
46.5 percentage of participants
|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
SD
|
31.0 percentage of participants
|
30.2 percentage of participants
|
45.5 percentage of participants
|
34.9 percentage of participants
|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
PD
|
1.4 percentage of participants
|
1.9 percentage of participants
|
7.3 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=99 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=101 Participants
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.
|
Trastuzumab+Pertuzumab
n=102 Participants
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.
|
Pertuzumab+Docetaxel
n=91 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
CR
|
23.2 percentage of participants
|
30.7 percentage of participants
|
16.7 percentage of participants
|
20.9 percentage of participants
|
|
Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
PR
|
56.6 percentage of participants
|
57.4 percentage of participants
|
51.0 percentage of participants
|
50.5 percentage of participants
|
|
Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
SD
|
20.2 percentage of participants
|
11.9 percentage of participants
|
30.4 percentage of participants
|
28.6 percentage of participants
|
|
Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
PD
|
0.0 percentage of participants
|
0.0 percentage of participants
|
2.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=97 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=100 Participants
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.
|
Trastuzumab+Pertuzumab
n=98 Participants
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.
|
Pertuzumab+Docetaxel
n=88 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
SD
|
17.5 percentage of participants
|
12.0 percentage of participants
|
31.6 percentage of participants
|
26.1 percentage of participants
|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
CR
|
21.6 percentage of participants
|
25.0 percentage of participants
|
11.2 percentage of participants
|
15.9 percentage of participants
|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
PR
|
59.8 percentage of participants
|
63.0 percentage of participants
|
55.1 percentage of participants
|
58.0 percentage of participants
|
|
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
PD
|
1.0 percentage of participants
|
0.0 percentage of participants
|
2.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=71 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=58 Participants
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.
|
Trastuzumab+Pertuzumab
n=61 Participants
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.
|
Pertuzumab+Docetaxel
n=47 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography
Primary Breast Tumor (n=71,58,61,47)
|
67.6 percentage of participants
Interval 55.5 to 78.2
|
65.5 percentage of participants
Interval 51.9 to 77.5
|
49.2 percentage of participants
Interval 36.1 to 62.3
|
66.0 percentage of participants
Interval 50.7 to 79.1
|
|
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography
Overall Response (n=71,53,55,43)
|
67.6 percentage of participants
Interval 55.5 to 78.2
|
67.9 percentage of participants
Interval 53.7 to 80.1
|
47.3 percentage of participants
Interval 33.7 to 61.2
|
65.1 percentage of participants
Interval 49.1 to 79.0
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=99 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=101 Participants
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.
|
Trastuzumab+Pertuzumab
n=102 Participants
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.
|
Pertuzumab+Docetaxel
n=91 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination
Primary Breast Tumor (n=99,101,102,91)
|
79.8 percentage of participants
Interval 70.5 to 87.2
|
88.1 percentage of participants
Interval 80.2 to 93.7
|
67.6 percentage of participants
Interval 57.7 to 76.6
|
71.4 percentage of participants
Interval 61.0 to 80.4
|
|
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination
Overall Response (n=97,100,98,88)
|
81.4 percentage of participants
Interval 72.3 to 88.6
|
88.0 percentage of participants
Interval 80.0 to 93.6
|
66.3 percentage of participants
Interval 56.1 to 75.6
|
73.9 percentage of participants
Interval 63.4 to 82.7
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=99 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=101 Participants
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.
|
Trastuzumab+Pertuzumab
n=102 Participants
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.
|
Pertuzumab+Docetaxel
n=91 Participants
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.
|
|---|---|---|---|---|
|
Time to Clinical Response During Neo-Adjuvant Treatment Period
|
6.3 months
Interval 6.0 to 7.0
|
6.3 months
Interval 4.0 to 7.0
|
6.9 months
Interval 6.0 to 9.0
|
7.3 months
Interval 6.0 to 9.0
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 monthsPopulation: ITT Population; Analysis was performed according to initial randomization.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period
|
0.0 percentage of participants
Interval 0.0 to 3.4
|
0.9 percentage of participants
Interval 0.0 to 5.1
|
7.5 percentage of participants
Interval 3.3 to 14.2
|
2.1 percentage of participants
Interval 0.3 to 7.3
|
SECONDARY outcome
Timeframe: Surgery (Within 2 weeks after Cycle 4) Up to approximately 24 monthsPopulation: ITT Population; Analysis was performed according to initial randomization. Number of participants analyzed = participants evaluable for this outcome.
Breast Conserving Surgery (BCS) was defined as quadrantectomy, lumpectomy, no surgery, sentinel node biopsy, axillary surgical resection or other method of avoiding mastectomy.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=62 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=56 Participants
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.
|
Trastuzumab+Pertuzumab
n=61 Participants
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.
|
Pertuzumab+Docetaxel
n=60 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned
|
22.6 percentage of participants
Interval 12.9 to 35.0
|
23.2 percentage of participants
Interval 13.0 to 36.4
|
18.0 percentage of participants
Interval 9.4 to 30.0
|
31.7 percentage of participants
Interval 20.3 to 45.0
|
SECONDARY outcome
Timeframe: Randomization up to a maximum of 329 weeksPopulation: ITT Population; Analysis was performed according to initial randomization.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Who Were Progression Free and Disease Free
Progression Free
|
82.2 percentage of participants
|
84.1 percentage of participants
|
74.8 percentage of participants
|
75.0 percentage of participants
|
|
Percentage of Participants Who Were Progression Free and Disease Free
Disease Free
|
82.5 percentage of participants
|
85.1 percentage of participants
|
80.2 percentage of participants
|
76.1 percentage of participants
|
SECONDARY outcome
Timeframe: Randomization up to a maximum of 329 weeksPopulation: ITT Population; Analysis was performed according to initial randomization.
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.
Outcome measures
| Measure |
Trastuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab+Docetaxel
n=107 Participants
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.
|
Trastuzumab+Pertuzumab
n=107 Participants
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.
|
Pertuzumab+Docetaxel
n=96 Participants
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.
|
|---|---|---|---|---|
|
Progression Free and Disease Free Survival
PFS
|
NA percentage of participants
Median and corresponding 80% confidence interval were not achieved due to o the low number of events in this participant population, as expected.
|
71.0 percentage of participants
Interval 71.0 to 76.0
|
NA percentage of participants
Median and corresponding 80% confidence interval were not achieved due to o the low number of events in this participant population, as expected.
|
NA percentage of participants
Median and corresponding 80% confidence interval were not achieved due to o the low number of events in this participant population, as expected.
|
|
Progression Free and Disease Free Survival
DFS
|
NA percentage of participants
Median and corresponding 80% confidence interval were not achieved due to o the low number of events in this participant population, as expected.
|
67.2 percentage of participants
Interval 67.0 to 72.0
|
NA percentage of participants
Median and corresponding 80% confidence interval were not achieved due to o the low number of events in this participant population, as expected.
|
NA percentage of participants
Median and corresponding 80% confidence interval were not achieved due to o the low number of events in this participant population, as expected.
|
Adverse Events
Trastuzumab+Pertuzumab+Docetaxel
Serious events: 22 serious events
Other events: 105 other events
Deaths: 0 deaths
Trastuzumab+Pertuzumab
Serious events: 19 serious events
Other events: 101 other events
Deaths: 0 deaths
Pertuzumab+Docetaxel
Serious events: 21 serious events
Other events: 94 other events
Deaths: 0 deaths
Trastuzumab+Docetaxel
Serious events: 21 serious events
Other events: 107 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Trastuzumab+Pertuzumab+Docetaxel
n=107 participants at risk
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.
|
Trastuzumab+Pertuzumab
n=108 participants at risk
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.
|
Pertuzumab+Docetaxel
n=94 participants at risk
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.
|
Trastuzumab+Docetaxel
n=107 participants at risk
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.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.8%
12/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
9.3%
10/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Neutropenic infection
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Pyelonephritis acute
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Wound infection
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Breast abscess
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Device related infection
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
H1N1 influenza
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Infection
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Sepsis
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Septic shock
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Pyrexia
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Imparied healing
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Abdominal strangulated hernia
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Cardiac disorders
Left ventricular dysfunction
|
2.8%
3/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Cardiac disorders
Angina pectoris
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Reproductive system and breast disorders
Ovarian cyst ruptured
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Reproductive system and breast disorders
Ovarian disorder
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Reproductive system and breast disorders
Uterine haemorrhage
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Hepatobiliary disorders
Hepatitis fulminant
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Immune system disorders
Drug hypersensitivity
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Nervous system disorders
Dural arteriovenous fistula
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Vascular disorders
Venous insufficiency
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
Other adverse events
| Measure |
Trastuzumab+Pertuzumab+Docetaxel
n=107 participants at risk
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.
|
Trastuzumab+Pertuzumab
n=108 participants at risk
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.
|
Pertuzumab+Docetaxel
n=94 participants at risk
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.
|
Trastuzumab+Docetaxel
n=107 participants at risk
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.
|
|---|---|---|---|---|
|
Eye disorders
Lacrimation increased
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
General Disorder
|
15.0%
16/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.9%
15/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
27.7%
26/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
15.9%
17/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Nausea
|
66.4%
71/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
48.1%
52/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
64.9%
61/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
65.4%
70/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
51.4%
55/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
42.6%
46/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
55.3%
52/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
37.4%
40/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Vomiting
|
36.4%
39/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
28.7%
31/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
39.4%
37/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
29.0%
31/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Stomatitis
|
20.6%
22/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
19.4%
21/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.7%
11/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.2%
12/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.1%
12/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.8%
12/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Constipation
|
13.1%
14/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.3%
9/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.2%
12/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Abdominal pain
|
10.3%
11/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
8/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
10.6%
10/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Haemorrhoids
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
8/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.3%
4/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Dyspepsia
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
68.2%
73/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
54.6%
59/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
69.1%
65/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
70.1%
75/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
28.0%
30/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
20.4%
22/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
31.9%
30/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
24.3%
26/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
12.1%
13/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
14.8%
16/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.8%
13/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
15.9%
17/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
9.3%
10/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.5%
8/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.7%
11/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
7/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Acne
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.3%
4/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.1%
2/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Fatigue
|
32.7%
35/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
31.5%
34/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
39.4%
37/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
32.7%
35/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Mucosal inflammation
|
30.8%
33/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
16.7%
18/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
29.8%
28/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
26.2%
28/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Asthenia
|
27.1%
29/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
17.6%
19/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
24.5%
23/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
20.6%
22/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Pyrexia
|
23.4%
25/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
19.4%
21/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
14.9%
14/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
15.0%
16/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Oedema peripheral
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
16.7%
18/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
9.6%
9/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.2%
12/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Chills
|
3.7%
4/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
9.3%
10/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.1%
2/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Chest pain
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Pain
|
2.8%
3/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
7/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
General disorders
Oedema
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.3%
4/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Blood and lymphatic system disorders
Neutropenia
|
59.8%
64/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
42.6%
46/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
71.3%
67/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
74.8%
80/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Blood and lymphatic system disorders
Leukopenia
|
12.1%
13/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.0%
13/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
16.0%
15/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
22.4%
24/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Blood and lymphatic system disorders
Anaemia
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
10.2%
11/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.8%
12/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
23.4%
25/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
26.9%
29/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
23.4%
22/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
22.4%
24/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.8%
18/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.0%
13/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
20.2%
19/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
15.0%
16/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.1%
13/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.6%
5/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.7%
11/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.1%
13/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
10.3%
11/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.5%
8/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.1%
13/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
8/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.7%
11/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Nervous system disorders
Headache
|
13.1%
14/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
23.1%
25/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
23.4%
22/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
15.9%
17/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Nervous system disorders
Dysgeusia
|
15.0%
16/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.0%
14/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
10.6%
10/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
15.0%
16/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
9.3%
10/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.9%
15/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
14.9%
14/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.1%
14/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Nervous system disorders
Dizziness
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.0%
14/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.5%
8/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Nervous system disorders
Neuropathy peripheral
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
9.3%
10/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Nervous system disorders
Paraesthesia
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
17.8%
19/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
20.4%
22/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
25.5%
24/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
19.6%
21/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
8/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.5%
8/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Seroma
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
2.8%
3/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.1%
2/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Injury, poisoning and procedural complications
Incision site pain
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.93%
1/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
17.6%
19/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
12.8%
12/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
10.3%
11/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.3%
11/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
10.6%
10/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.3%
4/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
10.2%
11/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.8%
13/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.2%
12/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Nasopharyngitis
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.2%
12/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Pharyngitis
|
3.7%
4/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.5%
8/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Infections and infestations
Urinary tract infection
|
3.7%
4/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.8%
3/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Vascular disorders
Hot flush
|
11.2%
12/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
8/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
7/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
10.3%
11/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Vascular disorders
Lymphoedema
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.1%
12/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Vascular disorders
Flushing
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.6%
5/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Vascular disorders
Hypertension
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.2%
3/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.8%
18/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.9%
15/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
24.5%
23/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
17.8%
19/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Psychiatric disorders
Insomnia
|
12.1%
13/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
7.4%
8/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
14.9%
14/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
13.1%
14/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Psychiatric disorders
Anxiety
|
2.8%
3/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.6%
6/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
0.00%
0/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Investigations
Alanine aminotransferase increased
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Investigations
Weight increased
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.3%
9/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.1%
1/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
3.7%
4/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
2.1%
2/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
8.4%
9/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Cardiac disorders
Palpitations
|
4.7%
5/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Cardiac disorders
Left ventricular dysfunction
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
5.3%
5/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Reproductive system and breast disorders
Menstruation irregular
|
3.7%
4/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
9.3%
10/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
9.6%
9/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.5%
7/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
|
Immune system disorders
Drug hypersensitivity
|
5.6%
6/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
11.1%
12/108 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
6.4%
6/94 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
1.9%
2/107 • Adverse events were recorded from the date of Screening until the clinical cut off date 20th October 2014 up to 7 years.
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER