Trial Outcomes & Findings for A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer (NCT NCT03493854)
NCT ID: NCT03493854
Last Updated: 2024-06-26
Results Overview
The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
500 participants
Primary outcome timeframe
Pre-dose on Cycle 8, Day 1 (up to 21 weeks)
Results posted on
2024-06-26
Participant Flow
A total of 607 patients were screened, 500 of whom were randomized.
Participant milestones
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 (neo)adjuvant anti-HER2 treatment cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 (neo)adjuvant anti-HER2 treatment cycles.
|
|---|---|---|
|
Neoadjuvant Treatment Phase (24 Weeks)
STARTED
|
252
|
248
|
|
Neoadjuvant Treatment Phase (24 Weeks)
Received at Least One Dose of Study Drug
|
252
|
248
|
|
Neoadjuvant Treatment Phase (24 Weeks)
COMPLETED
|
242
|
234
|
|
Neoadjuvant Treatment Phase (24 Weeks)
NOT COMPLETED
|
10
|
14
|
|
Surgery & Adjuvant Treatment (42 Weeks)
STARTED
|
242
|
234
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Completed Surgery
|
239
|
234
|
|
Surgery & Adjuvant Treatment (42 Weeks)
COMPLETED
|
209
|
217
|
|
Surgery & Adjuvant Treatment (42 Weeks)
NOT COMPLETED
|
33
|
17
|
|
Treatment-Free Follow-Up (up to 3 Years)
STARTED
|
247
|
241
|
|
Treatment-Free Follow-Up (up to 3 Years)
COMPLETED
|
223
|
219
|
|
Treatment-Free Follow-Up (up to 3 Years)
NOT COMPLETED
|
24
|
22
|
Reasons for withdrawal
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 (neo)adjuvant anti-HER2 treatment cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 (neo)adjuvant anti-HER2 treatment cycles.
|
|---|---|---|
|
Neoadjuvant Treatment Phase (24 Weeks)
Adverse Event
|
3
|
5
|
|
Neoadjuvant Treatment Phase (24 Weeks)
Death
|
1
|
1
|
|
Neoadjuvant Treatment Phase (24 Weeks)
Protocol Violation
|
0
|
1
|
|
Neoadjuvant Treatment Phase (24 Weeks)
Withdrawal by Subject
|
1
|
2
|
|
Neoadjuvant Treatment Phase (24 Weeks)
Progressive Disease
|
3
|
3
|
|
Neoadjuvant Treatment Phase (24 Weeks)
Other
|
1
|
0
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Adverse Event
|
12
|
7
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Lack of Efficacy
|
0
|
2
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Progressive Disease
|
4
|
0
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Withdrawal by Subject
|
2
|
2
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Other
|
7
|
2
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Death
|
1
|
1
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Physician Decision
|
3
|
2
|
|
Surgery & Adjuvant Treatment (42 Weeks)
Disease Relapse
|
4
|
1
|
|
Treatment-Free Follow-Up (up to 3 Years)
Death
|
10
|
11
|
|
Treatment-Free Follow-Up (up to 3 Years)
Withdrawal by Subject
|
10
|
10
|
|
Treatment-Free Follow-Up (up to 3 Years)
Lost to Follow-up
|
4
|
1
|
Baseline Characteristics
A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer
Baseline characteristics by cohort
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
Total
n=500 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.3 Years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
51.7 Years
STANDARD_DEVIATION 10.7 • n=7 Participants
|
51.0 Years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
250 Participants
n=5 Participants
|
248 Participants
n=7 Participants
|
498 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
32 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
200 Participants
n=5 Participants
|
189 Participants
n=7 Participants
|
389 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
20 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
54 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
164 Participants
n=5 Participants
|
165 Participants
n=7 Participants
|
329 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
19 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Randomization Stratification Factors: Hormone Receptor Status
ER Negative and PgR Negative
|
97 Participants
n=5 Participants
|
96 Participants
n=7 Participants
|
193 Participants
n=5 Participants
|
|
Randomization Stratification Factors: Hormone Receptor Status
ER Positive and PgR Positive
|
155 Participants
n=5 Participants
|
151 Participants
n=7 Participants
|
306 Participants
n=5 Participants
|
|
Randomization Stratification Factors: Hormone Receptor Status
Unknown
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Randomization Stratification Factors: Clinical Stage at Presentation
Stage II-IIIA
|
201 Participants
n=5 Participants
|
198 Participants
n=7 Participants
|
399 Participants
n=5 Participants
|
|
Randomization Stratification Factors: Clinical Stage at Presentation
Stage IIIB-IIIC
|
51 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
|
Randomization Stratification Factors: Neoadjuvant Chemotherapy Regimen
ddAC Followed by Paclitaxel
|
120 Participants
n=5 Participants
|
120 Participants
n=7 Participants
|
240 Participants
n=5 Participants
|
|
Randomization Stratification Factors: Neoadjuvant Chemotherapy Regimen
AC Followed by Docetaxel
|
132 Participants
n=5 Participants
|
128 Participants
n=7 Participants
|
260 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose on Cycle 8, Day 1 (up to 21 weeks)Population: Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.
The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=203 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=206 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)
|
72.4 micrograms per millilitre (μg/mL)
Geometric Coefficient of Variation 34.1
|
88.7 micrograms per millilitre (μg/mL)
Geometric Coefficient of Variation 33.6
|
SECONDARY outcome
Timeframe: Pre-dose on Cycle 8, Day 1 (up to 21 weeks)Population: Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.
The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=203 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=206 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)
|
43.2 micrograms per milllilitre (μg/mL)
Geometric Coefficient of Variation 34.7
|
57.5 micrograms per milllilitre (μg/mL)
Geometric Coefficient of Variation 37.0
|
SECONDARY outcome
Timeframe: Following completion of surgery (up to 33 weeks)Population: ITT Population: includes all enrolled participants.
Total pCR (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated. The lower bound of the CI will reliably reflect the largest tpCR difference that can be considered unlikely.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment
|
59.5 Percentage of participants
Interval 53.2 to 65.6
|
59.7 Percentage of participants
Interval 53.3 to 65.8
|
SECONDARY outcome
Timeframe: At 1, 2, 3, and 4 yearsPopulation: The analysis population included all participants who had undergone surgery. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=239 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=234 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria
1 Year
|
96.07 Percentage of participants
Interval 93.55 to 98.59
|
97.37 Percentage of participants
Interval 95.3 to 99.45
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria
2 Years
|
92.98 Percentage of participants
Interval 89.66 to 96.3
|
90.75 Percentage of participants
Interval 86.98 to 94.52
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria
3 Years
|
90.71 Percentage of participants
Interval 86.93 to 94.5
|
89.86 Percentage of participants
Interval 85.93 to 93.79
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria
4 Years
|
89.60 Percentage of participants
Interval 85.54 to 93.65
|
88.50 Percentage of participants
Interval 84.34 to 92.66
|
SECONDARY outcome
Timeframe: At 1, 2, 3, and 4 yearsPopulation: The analysis population included all participants who had undergone surgery. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
Invasive disease-free survival (iDFS) including second primary non-breast cancer (SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=239 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=234 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria
1 Year
|
95.63 Percentage of participants
Interval 92.99 to 98.28
|
96.94 Percentage of participants
Interval 94.7 to 99.17
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria
2 Years
|
92.10 Percentage of participants
Interval 88.6 to 95.6
|
89.44 Percentage of participants
Interval 85.44 to 93.43
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria
3 Years
|
89.39 Percentage of participants
Interval 85.37 to 93.4
|
88.54 Percentage of participants
Interval 84.4 to 92.69
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria
4 Years
|
88.27 Percentage of participants
Interval 84.01 to 92.53
|
87.64 Percentage of participants
Interval 83.35 to 91.93
|
SECONDARY outcome
Timeframe: At 1, 2, 3, and 4 yearsPopulation: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
Event-free survival (EFS) excluding second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria
1 Year
|
96.79 Percentage of participants
Interval 94.6 to 98.98
|
97.95 Percentage of participants
Interval 96.18 to 99.73
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria
2 Years
|
92.29 Percentage of participants
Interval 88.96 to 95.62
|
91.67 Percentage of participants
Interval 88.17 to 95.16
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria
3 Years
|
89.77 Percentage of participants
Interval 85.96 to 93.57
|
88.29 Percentage of participants
Interval 84.21 to 92.37
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria
4 Years
|
88.47 Percentage of participants
Interval 84.44 to 92.49
|
86.57 Percentage of participants
Interval 82.24 to 90.9
|
SECONDARY outcome
Timeframe: At 1, 2, 3, and 4 yearsPopulation: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
Event-free survival (EFS) including second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria
1 Year
|
96.38 Percentage of participants
Interval 94.06 to 98.7
|
97.54 Percentage of participants
Interval 95.59 to 99.48
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria
2 Years
|
91.47 Percentage of participants
Interval 87.98 to 94.96
|
90.41 Percentage of participants
Interval 86.69 to 94.14
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria
3 Years
|
88.53 Percentage of participants
Interval 84.52 to 92.53
|
87.04 Percentage of participants
Interval 82.78 to 91.3
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria
4 Years
|
87.22 Percentage of participants
Interval 83.02 to 91.43
|
85.75 Percentage of participants
Interval 81.31 to 90.18
|
SECONDARY outcome
Timeframe: At 1, 2, 3, and 4 yearsPopulation: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
The distant recurrence-free interval (DRFI) is defined as the time between randomization and the date of distant breast cancer recurrence.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria
1 Year
|
99.59 Percentage of participants
Interval 98.8 to 100.0
|
99.58 Percentage of participants
Interval 98.77 to 100.0
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria
2 Years
|
95.88 Percentage of participants
Interval 93.39 to 98.38
|
95.37 Percentage of participants
Interval 92.7 to 98.04
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria
3 Years
|
93.77 Percentage of participants
Interval 90.72 to 96.82
|
93.23 Percentage of participants
Interval 90.02 to 96.43
|
|
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria
4 Years
|
92.49 Percentage of participants
Interval 89.15 to 95.83
|
91.92 Percentage of participants
Interval 88.44 to 95.41
|
SECONDARY outcome
Timeframe: At 1, 2, 3, and 4 yearsPopulation: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
Overall survival is defined as the time from randomization to death from any cause.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
1 Year
|
99.60 Percentage of participants
Interval 98.82 to 100.0
|
99.19 Percentage of participants
Interval 98.06 to 100.0
|
|
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
2 Years
|
98.38 Percentage of participants
Interval 96.8 to 99.95
|
96.68 Percentage of participants
Interval 94.42 to 98.94
|
|
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
3 Years
|
96.73 Percentage of participants
Interval 94.5 to 98.96
|
95.83 Percentage of participants
Interval 93.3 to 98.36
|
|
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
4 Years
|
95.47 Percentage of participants
Interval 92.86 to 98.09
|
94.13 Percentage of participants
Interval 91.14 to 97.11
|
SECONDARY outcome
Timeframe: From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months)Population: Safety Population: includes all participants who received at least one dose of study medication.
The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Any Adverse Event (AE): Any Grade
|
251 Participants
|
248 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
AE with Fatal Outcome (Grade 5)
|
2 Participants
|
2 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Any AE: Grades 3 to 5
|
149 Participants
|
132 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Serious AE
|
52 Participants
|
49 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Related Serious AE
|
29 Participants
|
29 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Anaphylaxis and Hypersensitivity AEs, Any Grade
|
3 Participants
|
3 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Anaphylaxis and Hypersensitivity AEs, Grade ≥3
|
1 Participants
|
0 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Infusion/Admin.-Related Reactions Within 24 hrs, Any Grade
|
39 Participants
|
54 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Infusion/Admin.-Related Reactions Within 24 hrs, Grade ≥3
|
3 Participants
|
0 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Serious Rash/Skin Reactions, Any Grade
|
0 Participants
|
1 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Serious Rash/Skin Reactions, Grade ≥3
|
0 Participants
|
0 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Diarrhoea, Any Grade
|
149 Participants
|
153 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Diarrhoea, Grade ≥3
|
13 Participants
|
16 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Cardiac Dysfunction, Any Grade
|
65 Participants
|
52 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Cardiac Dysfunction, Grade ≥3
|
12 Participants
|
3 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Interstitial Lung Disease, Any Grade
|
3 Participants
|
5 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Interstitial Lung Disease, Grade ≥3
|
0 Participants
|
0 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Neutropenia/Febrile Neutropenia, Any Grade
|
142 Participants
|
123 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Neutropenia/Febrile Neutropenia, Grade ≥3
|
92 Participants
|
82 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Serious Mucositis, Any Grade
|
3 Participants
|
3 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Serious Mucositis, Grade ≥3
|
3 Participants
|
2 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
Pregnancy- and Neonatal-Related AEs, Any Grade
|
0 Participants
|
0 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
AE Leading to Study Drug Discontinuation
|
32 Participants
|
22 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
AE Leading to HER2-Targeted Therapy Discontinuation
|
15 Participants
|
12 Participants
|
|
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
AE Leading to Any Chemotherapy Drug Discontinuation
|
23 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks)Population: Safety Population: includes all participants who received at least one dose of study medication.
A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: Definite cardiac death (due to heart failure, myocardial infarction, or documented primary arrhythmia); or, Probable cardiac death (sudden unexpected death within 24 hours of a definite or probable cardiac event \[e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia\] without documented etiology).
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase
Any Primary Cardiac Event
|
0 Participants
|
2 Participants
|
|
Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase
Heart Failure and Significant LVEF Decline
|
0 Participants
|
1 Participants
|
|
Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase
Cardiac Death (Definite or Probable)
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks)Population: Safety Population: includes all participants who received at least one dose of study medication.
A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of \<50% confirmed by a second assessment within approximately 3 weeks.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase
Any Secondary Cardiac Event
|
4 Participants
|
1 Participants
|
|
Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase
Identified by Initial LVEF Assessment
|
4 Participants
|
1 Participants
|
|
Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase
Confirmed by Second LVEF Assessment
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From surgery until 28 days after the last dose of adjuvant treatment (42 weeks)Population: Safety Population: includes all participants who received at least one dose of study medication.
A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: Definite cardiac death (due to heart failure, myocardial infarction, or documented primary arrhythmia); or, Probable cardiac death (sudden unexpected death within 24 hours of a definite or probable cardiac event \[e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia\] without documented etiology).
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Number of Participants With a Primary Cardiac Event During the Adjuvant Phase
Any Primary Cardiac Event
|
1 Participants
|
2 Participants
|
|
Number of Participants With a Primary Cardiac Event During the Adjuvant Phase
Heart Failure and Significant LVEF Decline
|
1 Participants
|
2 Participants
|
|
Number of Participants With a Primary Cardiac Event During the Adjuvant Phase
Cardiac Death (Definite or Probable)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From surgery until 28 days after the last dose of adjuvant treatment (42 weeks)Population: Safety Population: includes all participants who received at least one dose of study medication.
A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of \<50% confirmed by a second assessment within approximately 3 weeks.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase
Any Secondary Cardiac Event
|
15 Participants
|
8 Participants
|
|
Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase
Identified by Initial LVEF Assessment
|
15 Participants
|
8 Participants
|
|
Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase
Confirmed by Second LVEF Assessment
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months)Population: Safety Population: includes all participants who received at least one dose of study medication. The number analyzed varies because it indicates all participants with a post-baseline laboratory value for a given test within the timeframe.
Clinical laboratory tests were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a participant with multiple post-baseline abnormalities, only the highest (worst) grade for a given laboratory test is reported. 'Any Grade' indicates the total number of participants with a post-baseline abnormality of any grade for the specified test.
Outcome measures
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 Participants
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Albumin, Low - Any Grade
|
50 Participants
|
39 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Albumin, Low - Grade 1
|
41 Participants
|
34 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Albumin, Low - Grade 2
|
8 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Albumin, Low - Grade 3
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Alkaline Phosphatase, High - Any Grade
|
80 Participants
|
71 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Alkaline Phosphatase, High - Grade 1
|
78 Participants
|
70 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Alkaline Phosphatase, High - Grade 2
|
2 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGPT/ALT, High - Any Grade
|
172 Participants
|
149 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGPT/ALT, High - Grade 1
|
145 Participants
|
132 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGPT/ALT, High - Grade 2
|
18 Participants
|
13 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGPT/ALT, High - Grade 3
|
9 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGOT/AST, High - Any Grade
|
149 Participants
|
130 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGOT/AST, High - Grade 1
|
137 Participants
|
125 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGOT/AST, High - Grade 2
|
7 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
SGOT/AST, High - Grade 3
|
5 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Creatinine, High - Any Grade
|
225 Participants
|
217 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Creatinine, High - Grade 1
|
214 Participants
|
204 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Creatinine, High - Grade 2
|
9 Participants
|
13 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Creatinine, High - Grade 3
|
2 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Glucose, Low - Any Grade
|
23 Participants
|
22 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Glucose, Low - Grade 1
|
20 Participants
|
22 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Glucose, Low - Grade 2
|
3 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Glucose, High - Any Grade
|
3 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Glucose, High - Grade 3
|
3 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Hemoglobin, Low - Any Grade
|
233 Participants
|
223 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Hemoglobin, Low - Grade 1
|
129 Participants
|
139 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Hemoglobin, Low - Grade 2
|
93 Participants
|
77 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Hemoglobin, Low - Grade 3
|
11 Participants
|
7 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Hemoglobin, High - Any Grade
|
12 Participants
|
6 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Hemoglobin, High - Grade 1
|
12 Participants
|
6 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Lymphocytes, Abs., Low - Any Grade
|
144 Participants
|
150 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Lymphocytes, Abs., Low - Grade 1
|
23 Participants
|
22 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Lymphocytes, Abs., Low - Grade 2
|
59 Participants
|
68 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Lymphocytes, Abs., Low - Grade 3
|
55 Participants
|
56 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Lymphocytes, Abs., Low - Grade 4
|
7 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Lymphocytes, Abs., High - Any Grade
|
4 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Lymphocytes, Abs., High - Grade 2
|
4 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Neutrophils, Total, Abs., Low - Any Grade
|
110 Participants
|
114 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Neutrophils, Total, Abs., Low - Grade 1
|
27 Participants
|
42 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Neutrophils, Total, Abs., Low - Grade 2
|
30 Participants
|
23 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Neutrophils, Total, Abs., Low - Grade 3
|
17 Participants
|
24 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Neutrophils, Total, Abs., Low - Grade 4
|
36 Participants
|
25 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Platelets, Low - Any Grade
|
72 Participants
|
67 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Platelets, Low - Grade 1
|
68 Participants
|
65 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Platelets, Low - Grade 2
|
3 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Platelets, Low - Grade 3
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, Low - Any Grade
|
45 Participants
|
41 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, Low - Grade 2
|
38 Participants
|
28 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, Low - Grade 3
|
6 Participants
|
11 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, Low - Grade 4
|
1 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, High - Any Grade
|
24 Participants
|
32 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, High - Grade 1
|
17 Participants
|
26 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, High - Grade 2
|
7 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, High - Grade 3
|
0 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Potassium, High - Grade 4
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, Low - Any Grade
|
27 Participants
|
33 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, Low - Grade 1
|
22 Participants
|
32 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, Low - Grade 3
|
4 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, Low - Grade 4
|
1 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, High - Any Grade
|
25 Participants
|
16 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, High - Grade 1
|
19 Participants
|
13 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, High - Grade 2
|
4 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, High - Grade 3
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Sodium, High - Grade 4
|
2 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Bilirubin, High - Any Grade
|
24 Participants
|
22 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Bilirubin, High - Grade 1
|
16 Participants
|
17 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Bilirubin, High - Grade 2
|
7 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Bilirubin, High - Grade 3
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Total Leukocyte Count, Low - Any Grade
|
199 Participants
|
203 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Total Leukocyte Count, Low - Grade 1
|
57 Participants
|
64 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Total Leukocyte Count, Low - Grade 2
|
81 Participants
|
78 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Total Leukocyte Count, Low - Grade 3
|
41 Participants
|
43 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Total Leukocyte Count, Low - Grade 4
|
20 Participants
|
18 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Total Leukocyte Count, High - Any Grade
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Total Leukocyte Count, High - Grade 1
|
0 Participants
|
1 Participants
|
Adverse Events
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
Serious events: 52 serious events
Other events: 251 other events
Deaths: 12 deaths
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
Serious events: 49 serious events
Other events: 248 other events
Deaths: 14 deaths
Serious adverse events
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 participants at risk
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 participants at risk
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.0%
10/252 • Number of events 11 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
3.6%
9/248 • Number of events 9 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Blood and lymphatic system disorders
Immune thrombocytopenia
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.2%
3/252 • Number of events 3 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Cardiac disorders
Cardiac failure
|
2.4%
6/252 • Number of events 6 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
1.6%
4/248 • Number of events 5 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Endocrine disorders
Goitre
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Anal incontinence
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Colitis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.79%
2/252 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Gastrointestinal toxicity
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Vomiting
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Chest pain
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Death
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Fatigue
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Lithiasis
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Mucosal inflammation
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Pyrexia
|
1.2%
3/252 • Number of events 4 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.81%
2/248 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Anal abscess
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Appendicitis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Cellulitis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Gastroenteritis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Influenza
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Laryngopharyngitis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Mastitis
|
0.79%
2/252 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Neutropenic sepsis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
1.2%
3/248 • Number of events 4 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Pneumonia
|
1.2%
3/252 • Number of events 3 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Postoperative abscess
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Postoperative wound infection
|
0.79%
2/252 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Pseudomonas infection
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Pyelonephritis acute
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Respiratory tract infection
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Sepsis
|
0.79%
2/252 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.81%
2/248 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Skin infection
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Urosepsis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Flap necrosis
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.79%
2/252 • Number of events 3 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
Clostridium test positive
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
Neutrophil count decreased
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
1.2%
3/248 • Number of events 3 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
White blood cell count decreased
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Periostitis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Angiosarcoma
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Clear cell renal cell carcinoma
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer stage I
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Seizure
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Syncope
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Psychiatric disorders
Depression
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Reproductive system and breast disorders
Breast haematoma
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Reproductive system and breast disorders
Breast inflammation
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Reproductive system and breast disorders
Intermenstrual bleeding
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Reproductive system and breast disorders
Uterine haemorrhage
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.81%
2/248 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.81%
2/248 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Vascular disorders
Embolism
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Vascular disorders
Haematoma
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Vascular disorders
Hypertension
|
0.00%
0/252 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.40%
1/248 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Vascular disorders
Iliac artery occlusion
|
0.40%
1/252 • Number of events 1 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
0.00%
0/248 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
Other adverse events
| Measure |
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
n=252 participants at risk
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.
|
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy
n=248 participants at risk
Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
43.3%
109/252 • Number of events 148 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
36.3%
90/248 • Number of events 117 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Blood and lymphatic system disorders
Leukopenia
|
14.3%
36/252 • Number of events 58 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
10.1%
25/248 • Number of events 42 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Blood and lymphatic system disorders
Neutropenia
|
25.4%
64/252 • Number of events 119 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
23.4%
58/248 • Number of events 109 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Eye disorders
Dry eye
|
3.6%
9/252 • Number of events 11 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
5.6%
14/248 • Number of events 14 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Eye disorders
Lacrimation increased
|
5.6%
14/252 • Number of events 15 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
5.6%
14/248 • Number of events 15 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Abdominal pain
|
6.0%
15/252 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.9%
22/248 • Number of events 29 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
21/252 • Number of events 25 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.1%
20/248 • Number of events 31 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Constipation
|
21.4%
54/252 • Number of events 79 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
23.0%
57/248 • Number of events 75 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Diarrhoea
|
58.7%
148/252 • Number of events 309 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
61.3%
152/248 • Number of events 293 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Dyspepsia
|
12.3%
31/252 • Number of events 34 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
14.1%
35/248 • Number of events 42 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Gastritis
|
2.0%
5/252 • Number of events 6 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
5.2%
13/248 • Number of events 14 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Haemorrhoids
|
4.4%
11/252 • Number of events 11 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.9%
22/248 • Number of events 22 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Nausea
|
62.3%
157/252 • Number of events 327 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
60.9%
151/248 • Number of events 308 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Stomatitis
|
24.2%
61/252 • Number of events 90 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
25.4%
63/248 • Number of events 85 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Gastrointestinal disorders
Vomiting
|
19.8%
50/252 • Number of events 73 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
20.2%
50/248 • Number of events 71 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Asthenia
|
33.3%
84/252 • Number of events 142 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
31.9%
79/248 • Number of events 160 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Fatigue
|
24.6%
62/252 • Number of events 114 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
28.6%
71/248 • Number of events 113 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Influenza like illness
|
4.4%
11/252 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.0%
15/248 • Number of events 21 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Injection site reaction
|
0.79%
2/252 • Number of events 2 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
16.1%
40/248 • Number of events 174 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Malaise
|
6.3%
16/252 • Number of events 20 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
5.6%
14/248 • Number of events 20 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Mucosal inflammation
|
19.4%
49/252 • Number of events 66 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
15.7%
39/248 • Number of events 53 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Oedema
|
5.2%
13/252 • Number of events 13 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
2.4%
6/248 • Number of events 6 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Oedema peripheral
|
10.3%
26/252 • Number of events 28 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
9.3%
23/248 • Number of events 25 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
General disorders
Pyrexia
|
16.3%
41/252 • Number of events 56 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
12.9%
32/248 • Number of events 41 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Cystitis
|
5.2%
13/252 • Number of events 14 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
3.2%
8/248 • Number of events 8 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
36/252 • Number of events 39 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
13.3%
33/248 • Number of events 40 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Paronychia
|
4.8%
12/252 • Number of events 14 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.1%
20/248 • Number of events 21 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Rhinitis
|
5.2%
13/252 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
5.6%
14/248 • Number of events 15 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Upper respiratory tract infection
|
9.5%
24/252 • Number of events 37 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
13.7%
34/248 • Number of events 43 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Infections and infestations
Urinary tract infection
|
6.3%
16/252 • Number of events 20 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
7.3%
18/248 • Number of events 22 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
14.3%
36/252 • Number of events 53 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
3.6%
9/248 • Number of events 9 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
9.9%
25/252 • Number of events 26 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
11.7%
29/248 • Number of events 31 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
21.4%
54/252 • Number of events 55 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
20.2%
50/248 • Number of events 51 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
Alanine aminotransferase increased
|
19.8%
50/252 • Number of events 61 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
15.7%
39/248 • Number of events 50 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
Aspartate aminotransferase increased
|
15.9%
40/252 • Number of events 54 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
11.7%
29/248 • Number of events 37 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
Ejection fraction decreased
|
9.5%
24/252 • Number of events 28 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.5%
16/248 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
Neutrophil count decreased
|
21.4%
54/252 • Number of events 141 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
16.1%
40/248 • Number of events 97 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
Weight decreased
|
6.0%
15/252 • Number of events 16 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
10.5%
26/248 • Number of events 27 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Investigations
White blood cell count decreased
|
13.9%
35/252 • Number of events 108 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
7.7%
19/248 • Number of events 58 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
20.2%
51/252 • Number of events 70 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
17.3%
43/248 • Number of events 50 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.7%
22/252 • Number of events 24 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.5%
16/248 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
32.5%
82/252 • Number of events 106 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
28.6%
71/248 • Number of events 91 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.0%
15/252 • Number of events 20 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
10.1%
25/248 • Number of events 32 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.2%
13/252 • Number of events 19 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.1%
20/248 • Number of events 24 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.1%
18/252 • Number of events 20 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.5%
21/248 • Number of events 23 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.2%
13/252 • Number of events 18 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
3.2%
8/248 • Number of events 9 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.6%
52/252 • Number of events 63 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
27.0%
67/248 • Number of events 80 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.9%
25/252 • Number of events 30 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.9%
22/248 • Number of events 26 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Dizziness
|
12.7%
32/252 • Number of events 39 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
13.7%
34/248 • Number of events 39 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Dysgeusia
|
13.9%
35/252 • Number of events 45 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
17.3%
43/248 • Number of events 53 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Headache
|
27.0%
68/252 • Number of events 84 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
18.1%
45/248 • Number of events 72 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Neuropathy peripheral
|
15.9%
40/252 • Number of events 53 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
13.3%
33/248 • Number of events 38 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Paraesthesia
|
9.1%
23/252 • Number of events 26 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
10.1%
25/248 • Number of events 30 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
15.9%
40/252 • Number of events 44 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
16.9%
42/248 • Number of events 45 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Psychiatric disorders
Anxiety
|
3.2%
8/252 • Number of events 8 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.0%
15/248 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Psychiatric disorders
Insomnia
|
13.9%
35/252 • Number of events 45 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
17.7%
44/248 • Number of events 50 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Reproductive system and breast disorders
Breast pain
|
5.2%
13/252 • Number of events 13 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.0%
15/248 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.9%
40/252 • Number of events 43 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
16.5%
41/248 • Number of events 44 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.0%
15/252 • Number of events 18 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
11.7%
29/248 • Number of events 32 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.7%
37/252 • Number of events 43 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
12.5%
31/248 • Number of events 36 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.6%
14/252 • Number of events 21 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.0%
15/248 • Number of events 16 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.2%
13/252 • Number of events 15 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.9%
17/248 • Number of events 22 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
73.0%
184/252 • Number of events 188 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
79.0%
196/248 • Number of events 196 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
5.6%
14/252 • Number of events 14 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
7.7%
19/248 • Number of events 20 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
13.5%
34/252 • Number of events 39 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
15.3%
38/248 • Number of events 43 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.6%
14/252 • Number of events 14 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
8.9%
22/248 • Number of events 26 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
6.7%
17/252 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
9.3%
23/248 • Number of events 23 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
6.7%
17/252 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.5%
16/248 • Number of events 18 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Onycholysis
|
5.2%
13/252 • Number of events 13 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
4.4%
11/248 • Number of events 11 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
5.2%
13/252 • Number of events 13 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
6.9%
17/248 • Number of events 17 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.9%
25/252 • Number of events 29 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
11.7%
29/248 • Number of events 35 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.2%
56/252 • Number of events 75 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
18.5%
46/248 • Number of events 56 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Vascular disorders
Hot flush
|
15.5%
39/252 • Number of events 44 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
16.5%
41/248 • Number of events 44 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
|
Vascular disorders
Hypertension
|
6.3%
16/252 • Number of events 19 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
4.8%
12/248 • Number of events 13 • Adverse events (AEs): From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months); All-cause mortality: From first dose of study treatment until end of follow-up (up to 4 years, 11 months)
After initiation of study drug, all AEs were reported until 28 days after the last dose of study drug. After this period, only drug-related serious AEs, heart failure, pregnancies, and malignancies were reported.
|
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 only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER