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A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer

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ClinicalTrials.gov Identifier: NCT00950300
Recruitment Status : Completed
First Posted : July 31, 2009
Results First Posted : January 23, 2017
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: 5-Fluorouracil
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Epirubicin
Drug: Herceptin IV [trastuzumab]
Drug: Herceptin SC [trastuzumab]
Enrollment 596
Recruitment Details  
Pre-assignment Details A total of 833 participants were screened, out of which, 596 participants were enrolled into the study.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 milligrams per meter-squared (mg/m^2) every 21 days for four cycles followed by 5-fluorouracil 500 mg/m^2, epirubicin 75 mg/m^2, and cyclophosphamide 500 mg/m^2 (FEC) every 21 days for four cycles. Herceptin was administered as 8 milligrams per kilogram (mg/kg) on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the Treatment-Free Follow-Up (TFFU) Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the Survival Follow-Up (SFU) Period. Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-milligram (mg) fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Period Title: Neoadjuvant/Adjuvant Treatment Periods
Started 299 297
Received Neoadjuvant Treatment 298 297
Underwent Surgery 277 273
Entered Adjuvant Treatment 277 274
Completed 257 255
Not Completed 42 42
Reason Not Completed
Adverse Event or Intercurrent Illness             6             15
Death             1             3
Insufficient Therapeutic Response             3             0
Violation of Selection Criteria             2             1
Protocol Violation             1             0
Participant Refusal/Withdrawal             4             5
Lost to Follow-up             2             1
Progression of Disease             12             11
Recurrence of Disease             10             5
Not Specified             1             1
Period Title: TFFU Period
Started 265 [1] 268 [1]
Completed 165 [2] 161 [2]
Not Completed 100 107
Reason Not Completed
Adverse Event or Intercurrent Illness             3             4
Death             4             1
Refused Treatment             10             11
Failure to Return             16             16
Recurrence of Disease             63             72
Not Specified             4             3
[1]
Participants could withdraw from the study entirely or advance directly to the TFFU or SFU Period.
[2]
Includes participants who completed either 2 years of follow-up or 5 years of follow-up.
Period Title: SFU Period
Started 118 [1] 123 [1]
Completed 40 [2] 45 [2]
Not Completed 78 78
Reason Not Completed
Death             44             42
Lost to Follow-up             30             28
Withdrawal by Subject             4             8
[1]
Participants could withdraw from the study entirely or advance directly to the SFU Period.
[2]
Includes participants who completed either 2 years of follow-up or 5 years of follow-up.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy Total
Hide Arm/Group Description Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period. Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period. Total of all reporting groups
Overall Number of Baseline Participants 297 294 591
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population: All participants with at least one efficacy assessment after administration of the first treatment cycle.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 297 participants 294 participants 591 participants
49.5  (10.83) 50.3  (11.08) 49.9  (10.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 297 participants 294 participants 591 participants
Female
297
 100.0%
294
 100.0%
591
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery
Hide Description Pre-dose samples were obtained prior to surgery (Cycle 8). The observed Ctrough was recorded, averaged among all participants, and expressed in micrograms per milliliter (μg/mL).
Time Frame Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary Pharmacokinetic (PK) Per Protocol (PP) Population: All participants with at least one measurable trastuzumab serum concentration and who did not have any major protocol violations related to PK sampling for the primary endpoint.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 235 234
Mean (Standard Deviation)
Unit of Measure: μg/mL
57.8  (30.3) 78.7  (43.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments PK sample size calculations based on percentage of coefficient of variation (CV%) for Ctrough of trastuzumab from previous metastatic breast cancer (MBC) and early breast cancer (EBC) studies. Because pre-surgery situation was comparable to MBC setting, interpatient CV% of 60 percent (%) was assumed and 130 participants per arm (260 participants total) were needed to demonstrate Ctrough comparability with 80% power if the true means of the two formulations did not differ by greater than (>) 5%.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was concluded if the lower limit of the 90% confidence interval (CI) was greater than or equal to (≥) 0.8 for the geometric mean ratio.
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.33
Confidence Interval (2-Sided) 90%
1.24 to 1.44
Estimation Comments Ratio of test treatment group (Herceptin SC + Chemotherapy) to reference treatment group (Herceptin IV + Chemotherapy).
2.Primary Outcome
Title Percentage of Participants With Pathological Complete Response (pCR)
Hide Description Participants were evaluated following eight cycles of treatment and after surgery to assess for pCR, defined as absence of neoplastic invasive cells in the breast according to pathologist examination. The percentage of participants with pCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.
Time Frame After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy (E) PP Population: All participants with at least one on-treatment efficacy assessment who received a full eight cycles of study treatment according to randomization and who met additional protocol-specified criteria.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 263 260
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40.7
(34.7 to 46.9)
45.4
(39.2 to 51.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments Assuming pCR rates of at least 40% in both arms, 552 participants were necessary to conclude non-inferiority in pCR rate with a power of 80% using a one-sided 97.5% CI for the difference of the response rates and a non-inferiority margin of 12.5%.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was concluded if the lower limit of the one-sided 97.5% CI was above -12.5% for the difference in response (pCR) rates.
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 4.70
Confidence Interval (1-Sided) 97.5%
-4.0
Estimation Comments The one-sided 97.5% CI for the difference in response (pCR) rates was calculated using the Anderson-Hauck continuity correction.
3.Secondary Outcome
Title Observed Ctrough of Trastuzumab After Surgery
Hide Description Pre-dose samples were obtained after surgery (Cycle 13). The observed Ctrough was recorded, averaged among all participants, and expressed in μg/mL.
Time Frame Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Secondary PKPP Population: All participants with at least one measurable trastuzumab serum concentration and who did not have any major protocol violations related to PK sampling for the secondary endpoint.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 223 227
Mean (Standard Deviation)
Unit of Measure: μg/mL
62.1  (37.1) 90.4  (41.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments Additional supportive analysis.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.51
Confidence Interval (2-Sided) 90%
1.40 to 1.63
Estimation Comments Ratio of test treatment group (Herceptin SC + Chemotherapy) to reference treatment group (Herceptin IV + Chemotherapy).
4.Secondary Outcome
Title Predicted Ctrough of Trastuzumab Prior to Surgery
Hide Description Predicted Ctrough at pre-dose prior to surgery (Cycle 8) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.
Time Frame Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKPP Population: All participants with at least one measurable trastuzumab serum concentration.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 276 278
Mean (Standard Deviation)
Unit of Measure: μg/mL
51.4  (19.4) 80.3  (33.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments Additional supportive analysis.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.55
Confidence Interval (2-Sided) 90%
1.46 to 1.64
Estimation Comments Ratio of test treatment group (Herceptin SC + Chemotherapy) to reference treatment group (Herceptin IV + Chemotherapy).
5.Secondary Outcome
Title Predicted Ctrough of Trastuzumab After Surgery
Hide Description Predicted Ctrough at pre-dose after surgery (Cycle 13) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.
Time Frame Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKPP Population; only participants with a Cycle 13 pre-dose PK measurement were included in the analysis.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 236 236
Mean (Standard Deviation)
Unit of Measure: μg/mL
51.7  (20.0) 80.6  (33.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments Additional supportive analysis.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 1.55
Confidence Interval (2-Sided) 90%
1.45 to 1.64
Estimation Comments Ratio of test treatment group (Herceptin SC + Chemotherapy) to reference treatment group (Herceptin IV + Chemotherapy).
6.Secondary Outcome
Title Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery
Hide Description Pre-dose samples were obtained prior to surgery (Cycle 8). The number of participants who had an observed Ctrough >20 μg/mL was reported.
Time Frame Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary PKPP Population
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 235 234
Measure Type: Number
Unit of Measure: participants
232 227
7.Secondary Outcome
Title Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery
Hide Description Pre-dose samples were obtained after surgery (Cycle 13). The number of participants who had an observed Ctrough >20 μg/mL was reported.
Time Frame Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Secondary PKPP Population
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 223 227
Measure Type: Number
Unit of Measure: participants
216 227
8.Secondary Outcome
Title Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery
Hide Description PK samples were obtained prior to surgery (Cycle 7). The Cmax during Cycle 7 was recorded, averaged among all participants, and expressed in μg/mL.
Time Frame Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary PKPP Population; only those participants who provided evaluable data were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 235 233
Mean (Standard Deviation)
Unit of Measure: μg/mL
221  (118) 149  (64.8)
9.Secondary Outcome
Title Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery
Hide Description PK samples were obtained prior to surgery (Cycle 7). The Tmax during Cycle 7 was recorded, averaged among all participants, and expressed in days.
Time Frame Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary PKPP Population; only those participants who provided evaluable data were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 235 233
Mean (Standard Deviation)
Unit of Measure: days
0.05  (0.04) 4.12  (2.91)
10.Secondary Outcome
Title Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery
Hide Description PK samples were obtained prior to surgery (Cycle 7). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 7 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in days multiplied by micrograms per milliliters (d*μg/mL).
Time Frame Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary PKPP Population; only those participants who provided evaluable data were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 235 233
Mean (Standard Deviation)
Unit of Measure: d*μg/mL
2056  (598) 2268  (875)
11.Secondary Outcome
Title Cmax of Trastuzumab After Surgery
Hide Description PK samples were obtained after surgery (Cycle 12). The Cmax during Cycle 12 was recorded, averaged among all participants, and expressed in μg/mL.
Time Frame Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
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Hide Analysis Population Description
Secondary PKPP Population; only those participants who provided evaluable data were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 223 223
Mean (Standard Deviation)
Unit of Measure: μg/mL
230  (118) 166  (58.8)
12.Secondary Outcome
Title Tmax of Trastuzumab After Surgery
Hide Description PK samples were obtained after surgery (Cycle 12). The Tmax during Cycle 12 was recorded, averaged among all participants, and expressed in days.
Time Frame Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
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Hide Analysis Population Description
Secondary PKPP Population; only those participants who provided evaluable data were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 223 222
Mean (Standard Deviation)
Unit of Measure: days
0.06  (0.13) 4.08  (2.87)
13.Secondary Outcome
Title AUC21d of Trastuzumab After Surgery
Hide Description PK samples were obtained after surgery (Cycle 12). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 12 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in d*μg/mL.
Time Frame Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
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Hide Analysis Population Description
Secondary PKPP Population; only those participants who provided evaluable data were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 223 223
Mean (Standard Deviation)
Unit of Measure: d*μg/mL
2179  (725) 2610  (945)
14.Secondary Outcome
Title Percentage of Participants With Total Pathological Complete Response (tpCR)
Hide Description Participants were evaluated following eight cycles of treatment and after surgery to assess for tpCR, defined as absence of neoplastic invasive cells in the breast and axillary lymph nodes according to pathologist examination. The percentage of participants with tpCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.
Time Frame After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
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Hide Analysis Population Description
EPP Population
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 263 260
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
34.2
(28.5 to 40.3)
39.2
(33.3 to 45.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 5.01
Confidence Interval (2-Sided) 95%
-3.5 to 13.5
Estimation Comments The 95% CI for the difference in response (tpCR) rates was calculated using the Anderson-Hauck continuity correction.
15.Secondary Outcome
Title Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline
Hide Description Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to less than (<) 10 millimeters (mm) with no prior assessment of progressive disease (PD). PR was defined as greater than or equal to (≥) 30% decrease from Baseline in sum diameter (SD) of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. The percentage of participants with overall response of CR or PR at the end of neoadjuvant treatment was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.
Time Frame Tumor assessments at Baseline; on Day 1 of Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months overall)
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Hide Analysis Population Description
EPP Population; only participants with measurable disease at Baseline were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 260 258
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
88.8
(84.4 to 92.4)
87.2
(82.5 to 91.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -1.64
Confidence Interval (2-Sided) 95%
-7.4 to 4.2
Estimation Comments The 95% CI for the difference in response (CR+PR) rates was calculated using the Anderson-Hauck continuity correction.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.50 to 1.46
Estimation Comments OR of test treatment group (Herceptin SC + Chemotherapy) to reference treatment group (Herceptin IV + Chemotherapy).
16.Secondary Outcome
Title Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline
Hide Description Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm with no prior assessment of PD. PR was defined as ≥30% decrease from Baseline in SD of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. Time to response was defined as the time from first dose of study medication to the first assessment of CR or PR, which was the date the response was first documented by objective evidence, among participants with an overall response of CR or PR.
Time Frame Tumor assessments at Baseline; on Day 1 Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of chemotherapy (approximately 6 months overall)
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Hide Analysis Population Description
EPP Population; only participants with measurable disease at Baseline and a response of CR or PR were included.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 231 225
Median (Full Range)
Unit of Measure: weeks
6.14
(3 to 25)
6.14
(3 to 28)
17.Secondary Outcome
Title Percentage of Participants Who Experienced a Protocol-Defined Event
Hide Description Protocol-defined events included disease recurrence/progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. The percentage of participants who experienced a protocol-defined event at any time during the study was reported.
Time Frame Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
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Hide Analysis Population Description
ITT Population
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 297 294
Measure Type: Number
Unit of Measure: percentage of participants
33.3 32.7
18.Secondary Outcome
Title Event-Free Survival (EFS)
Hide Description Protocol-defined events included disease recurrence or progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. EFS was estimated by Kaplan-Meier analysis and defined as the time from randomization to the first protocol-defined event.
Time Frame Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
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Hide Analysis Population Description
ITT Population
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 297 294
Median (Full Range)
Unit of Measure: months
NA [1] 
(1 to 82)
NA [1] 
(1 to 76)
[1]
The median time to event could not be determined because of a high number (>50%) of censored observations. Full range includes censored observations.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8651
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.74 to 1.29
Estimation Comments HR of test treatment group (Herceptin SC + Chemotherapy) to reference treatment group (Herceptin IV + Chemotherapy).
19.Secondary Outcome
Title Percentage of Participants Who Died
Hide Description The percentage of participants who died at any time during the study was reported.
Time Frame Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
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Hide Analysis Population Description
ITT Population
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 297 294
Measure Type: Number
Unit of Measure: percentage of participants
14.5 13.6
20.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was estimated by Kaplan-Meier analysis and defined as the time from randomization to death from any cause.
Time Frame Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
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Hide Analysis Population Description
ITT Population
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
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Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 297 294
Median (Full Range)
Unit of Measure: months
NA [1] 
(2 to 82)
NA [1] 
(3 to 79)
[1]
The median time to event could not be determined because of a high number (>50%) of censored observations. Full range includes censored observations.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin IV + Chemotherapy, Herceptin SC + Chemotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7767
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.61 to 1.45
Estimation Comments HR of test treatment group (Herceptin SC + Chemotherapy) to reference treatment group (Herceptin IV + Chemotherapy).
21.Secondary Outcome
Title Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab
Time Frame Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18
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Hide Analysis Population Description
Safety Population: All participants who received at least one dose of study medication. Here, Overall Number of Participants Analyzed = participants who were evaluable for this outcome measure.
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 296 295
Measure Type: Number
Unit of Measure: participants
Treatment-induced ADAs 28 46
Treatment-enhanced ADA 2 1
22.Secondary Outcome
Title Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)
Hide Description Participants in the Herceptin SC arm provided PK samples for evaluation of anti-rHuPH20 antibodies. The number of participants with “Treatment-induced ADAs” and “Treatment-enhanced ADA” against rHuPH20 (an excipient unique to the SC formulation) at any time during or after treatment was reported. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result (four-fold increase of titer).
Time Frame Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18
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Hide Analysis Population Description
Safety Population; as rHuPH20 is unique to SC formulation, this outcome measure was applicable for “Herceptin SC + Chemotherapy” arm only. Here, Overall Number of Participants Analyzed = participants who were evaluable for this outcome measure.
Arm/Group Title Herceptin SC + Chemotherapy
Hide Arm/Group Description:
Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
Overall Number of Participants Analyzed 295
Measure Type: Number
Unit of Measure: participants
Treatment-induced ADA 49
Treatment-enhanced ADA 13
Time Frame Approximately 87 months overall
Adverse Event Reporting Description Analysis was performed on Safety Population.
 
Arm/Group Title Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Hide Arm/Group Description Participants received eight cycles of Herceptin IV plus chemotherapy prior to surgery and ten cycles of Herceptin IV after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as 8 mg/kg on Day 1 and then as 6 mg/kg on Day 22 and every 21 days thereafter. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period. Participants received eight cycles of Herceptin SC plus chemotherapy prior to surgery and ten cycles of Herceptin SC after surgery. Chemotherapy consisted of docetaxel 75 mg/m^2 every 21 days for four cycles followed by FEC every 21 days for four cycles. Herceptin was administered as a 600-mg fixed dose given every 21 days. The first eight cycles prior to surgery comprised the Neoadjuvant Treatment Period, and the ten cycles of Herceptin IV after surgery comprised the Adjuvant Treatment Period. Thereafter, participants entered the TFFU Period. Participants who were withdrawn from the Neoadjuvant Treatment Period for any reason, or who experienced disease recurrence during either the Adjuvant Treatment Period or TFFU Period, could be entered into the SFU Period.
All-Cause Mortality
Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   45/298 (15.10%)   65/297 (21.89%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  10/298 (3.36%)  13/297 (4.38%) 
Neutropenia * 1  9/298 (3.02%)  7/297 (2.36%) 
Leukopenia * 1  0/298 (0.00%)  1/297 (0.34%) 
Thrombocytopenia * 1  0/298 (0.00%)  1/297 (0.34%) 
Lymphadenopathy * 1  1/298 (0.34%)  0/297 (0.00%) 
Cardiac disorders     
Cardiac failure congestive * 1  0/298 (0.00%)  2/297 (0.67%) 
Arrhythmia * 1  0/298 (0.00%)  1/297 (0.34%) 
Myocardial infarction * 1  1/298 (0.34%)  1/297 (0.34%) 
Angina pectoris * 1  1/298 (0.34%)  0/297 (0.00%) 
Atrial fibrillation * 1  0/298 (0.00%)  1/297 (0.34%) 
Coronary artery disease * 1  1/298 (0.34%)  0/297 (0.00%) 
Myocardial ischaemia * 1  0/298 (0.00%)  1/297 (0.34%) 
Endocrine disorders     
Goitre * 1  1/298 (0.34%)  0/297 (0.00%) 
Gastrointestinal disorders     
Haemorrhoids * 1  1/298 (0.34%)  1/297 (0.34%) 
Nausea * 1  1/298 (0.34%)  1/297 (0.34%) 
Diarrhoea * 1  1/298 (0.34%)  0/297 (0.00%) 
Vomiting * 1  1/298 (0.34%)  0/297 (0.00%) 
General disorders     
Pyrexia * 1  0/298 (0.00%)  2/297 (0.67%) 
General physical health deterioration * 1  0/298 (0.00%)  1/297 (0.34%) 
Sudden death * 1  0/298 (0.00%)  1/297 (0.34%) 
Death * 1  1/298 (0.34%)  0/297 (0.00%) 
Immune system disorders     
Hypersensitivity * 1  2/298 (0.67%)  0/297 (0.00%) 
Infections and infestations     
Respiratory tract infection viral * 1  0/298 (0.00%)  1/297 (0.34%) 
Tonsillitis * 1  0/298 (0.00%)  2/297 (0.67%) 
Pneumonia * 1  4/298 (1.34%)  2/297 (0.67%) 
Atypical pneumonia * 1  0/298 (0.00%)  1/297 (0.34%) 
Cellulitis * 1  0/298 (0.00%)  2/297 (0.67%) 
Febrile infection * 1  1/298 (0.34%)  0/297 (0.00%) 
Gastroenteritis * 1  1/298 (0.34%)  0/297 (0.00%) 
H1N1 influenza * 1  1/298 (0.34%)  0/297 (0.00%) 
Hepatitis B * 1  1/298 (0.34%)  0/297 (0.00%) 
Lower respiratory tract infection * 1  0/298 (0.00%)  2/297 (0.67%) 
Periorbital cellulitis * 1  0/298 (0.00%)  1/297 (0.34%) 
Postoperative wound infection * 1  0/298 (0.00%)  2/297 (0.67%) 
Respiratory tract infection * 1  0/298 (0.00%)  1/297 (0.34%) 
Septic shock * 1  0/298 (0.00%)  1/297 (0.34%) 
Urinary tract infection * 1  1/298 (0.34%)  0/297 (0.00%) 
Cystitis * 1  0/298 (0.00%)  1/297 (0.34%) 
Abscess * 1  0/298 (0.00%)  1/297 (0.34%) 
Encephalitis viral * 1  0/298 (0.00%)  1/297 (0.34%) 
Herpes zoster * 1  0/298 (0.00%)  1/297 (0.34%) 
Infected lymphocele * 1  1/298 (0.34%)  0/297 (0.00%) 
Infection * 1  1/298 (0.34%)  0/297 (0.00%) 
Post procedural infection * 1  0/298 (0.00%)  1/297 (0.34%) 
Pyelonephritis acute * 1  0/298 (0.00%)  1/297 (0.34%) 
Sepsis * 1  0/298 (0.00%)  1/297 (0.34%) 
Wound infection * 1  0/298 (0.00%)  1/297 (0.34%) 
Mastitis * 1  1/298 (0.34%)  1/297 (0.34%) 
Tonsillitis bacterial * 1  0/298 (0.00%)  1/297 (0.34%) 
Breast abscess * 1  1/298 (0.34%)  1/297 (0.34%) 
Injury, poisoning and procedural complications     
Post procedural haematoma * 1  1/298 (0.34%)  0/297 (0.00%) 
Radius fracture * 1  1/298 (0.34%)  1/297 (0.34%) 
Humerus fracture * 1  1/298 (0.34%)  0/297 (0.00%) 
Incision site haematoma * 1  1/298 (0.34%)  0/297 (0.00%) 
Lumbar vertebral fracture * 1  0/298 (0.00%)  1/297 (0.34%) 
Pulmonary radiation injury * 1  0/298 (0.00%)  1/297 (0.34%) 
Radiation pneumonitis * 1  1/298 (0.34%)  0/297 (0.00%) 
Investigations     
Tumour marker increased * 1  0/298 (0.00%)  1/297 (0.34%) 
Ejection fraction * 1  0/298 (0.00%)  1/297 (0.34%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  0/298 (0.00%)  1/297 (0.34%) 
Spinal pain * 1  0/298 (0.00%)  1/297 (0.34%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Endometrial cancer * 1  0/298 (0.00%)  2/297 (0.67%) 
Myeloid leukaemia * 1  1/298 (0.34%)  0/297 (0.00%) 
Thyroid cancer * 1  0/298 (0.00%)  1/297 (0.34%) 
Nervous system disorders     
Dizziness * 1  0/298 (0.00%)  1/297 (0.34%) 
Cerebrovascular accident * 1  0/298 (0.00%)  1/297 (0.34%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous * 1  0/298 (0.00%)  1/297 (0.34%) 
Pregnancy * 1  0/298 (0.00%)  1/297 (0.34%) 
Psychiatric disorders     
Anxiety * 1  1/298 (0.34%)  0/297 (0.00%) 
Depression * 1  0/298 (0.00%)  1/297 (0.34%) 
Schizophrenia * 1  0/298 (0.00%)  1/297 (0.34%) 
Renal and urinary disorders     
Renal colic * 1  0/298 (0.00%)  1/297 (0.34%) 
Reproductive system and breast disorders     
Menorrhagia * 1  0/298 (0.00%)  1/297 (0.34%) 
Ovarian haemorrhage * 1  0/298 (0.00%)  1/297 (0.34%) 
Ovarian mass * 1  1/298 (0.34%)  0/297 (0.00%) 
Vaginal prolapse * 1  0/298 (0.00%)  1/297 (0.34%) 
Respiratory, thoracic and mediastinal disorders     
Pneumothorax * 1  1/298 (0.34%)  0/297 (0.00%) 
Emphysema * 1  1/298 (0.34%)  0/297 (0.00%) 
Pleural effusion * 1  0/298 (0.00%)  2/297 (0.67%) 
Pulmonary embolism * 1  0/298 (0.00%)  2/297 (0.67%) 
Skin and subcutaneous tissue disorders     
Erythema multiforme * 1  0/298 (0.00%)  1/297 (0.34%) 
Vascular disorders     
Lymphorrhoea * 1  0/298 (0.00%)  1/297 (0.34%) 
Haematoma * 1  1/298 (0.34%)  1/297 (0.34%) 
Thrombophlebitis * 1  0/298 (0.00%)  1/297 (0.34%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (19.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Herceptin IV + Chemotherapy Herceptin SC + Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   277/298 (92.95%)   283/297 (95.29%) 
Blood and lymphatic system disorders     
Neutropenia * 1  135/298 (45.30%)  128/297 (43.10%) 
Leukopenia * 1  46/298 (15.44%)  30/297 (10.10%) 
Anaemia * 1  41/298 (13.76%)  34/297 (11.45%) 
Gastrointestinal disorders     
Nausea * 1  147/298 (49.33%)  145/297 (48.82%) 
Diarrhoea * 1  109/298 (36.58%)  101/297 (34.01%) 
Vomiting * 1  69/298 (23.15%)  69/297 (23.23%) 
Stomatitis * 1  51/298 (17.11%)  57/297 (19.19%) 
Constipation * 1  45/298 (15.10%)  43/297 (14.48%) 
Dyspepsia * 1  30/298 (10.07%)  33/297 (11.11%) 
Abdominal pain upper * 1  27/298 (9.06%)  21/297 (7.07%) 
Abdominal pain * 1  16/298 (5.37%)  22/297 (7.41%) 
General disorders     
Asthenia * 1  75/298 (25.17%)  75/297 (25.25%) 
Fatigue * 1  80/298 (26.85%)  70/297 (23.57%) 
Mucosal inflammation * 1  39/298 (13.09%)  31/297 (10.44%) 
Pyrexia * 1  35/298 (11.74%)  35/297 (11.78%) 
Oedema peripheral * 1  30/298 (10.07%)  23/297 (7.74%) 
Injection site pain * 1  0/298 (0.00%)  18/297 (6.06%) 
Oedema * 1  15/298 (5.03%)  10/297 (3.37%) 
Pain * 1  15/298 (5.03%)  12/297 (4.04%) 
Infections and infestations     
Nasopharyngitis * 1  40/298 (13.42%)  24/297 (8.08%) 
Upper respiratory tract infection * 1  30/298 (10.07%)  30/297 (10.10%) 
Urinary tract infection * 1  22/298 (7.38%)  10/297 (3.37%) 
Pharyngitis * 1  11/298 (3.69%)  15/297 (5.05%) 
Injury, poisoning and procedural complications     
Incision site pain * 1  24/298 (8.05%)  33/297 (11.11%) 
Procedural pain * 1  16/298 (5.37%)  18/297 (6.06%) 
Radiation skin injury * 1  34/298 (11.41%)  41/297 (13.80%) 
Investigations     
Alanine aminotransferase increased * 1  19/298 (6.38%)  16/297 (5.39%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  59/298 (19.80%)  58/297 (19.53%) 
Musculoskeletal and connective tissue disorders     
Myalgia * 1  54/298 (18.12%)  61/297 (20.54%) 
Arthralgia * 1  60/298 (20.13%)  53/297 (17.85%) 
Musculoskeletal pain * 1  22/298 (7.38%)  18/297 (6.06%) 
Back pain * 1  25/298 (8.39%)  26/297 (8.75%) 
Pain in extremity * 1  26/298 (8.72%)  29/297 (9.76%) 
Bone pain * 1  10/298 (3.36%)  19/297 (6.40%) 
Nervous system disorders     
Headache * 1  44/298 (14.77%)  50/297 (16.84%) 
Peripheral sensory neuropathy * 1  27/298 (9.06%)  33/297 (11.11%) 
Dysgeusia * 1  22/298 (7.38%)  24/297 (8.08%) 
Dizziness * 1  28/298 (9.40%)  29/297 (9.76%) 
Neuropathy peripheral * 1  18/298 (6.04%)  24/297 (8.08%) 
Psychiatric disorders     
Insomnia * 1  31/298 (10.40%)  26/297 (8.75%) 
Reproductive system and breast disorders     
Amenorrhoea * 1  10/298 (3.36%)  15/297 (5.05%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  24/298 (8.05%)  35/297 (11.78%) 
Epistaxis * 1  18/298 (6.04%)  19/297 (6.40%) 
Dyspnoea * 1  22/298 (7.38%)  21/297 (7.07%) 
Oropharyngeal pain * 1  19/298 (6.38%)  19/297 (6.40%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  188/298 (63.09%)  187/297 (62.96%) 
Rash * 1  44/298 (14.77%)  48/297 (16.16%) 
Nail disorder * 1  31/298 (10.40%)  29/297 (9.76%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  18/298 (6.04%)  20/297 (6.73%) 
Pruritus * 1  27/298 (9.06%)  26/297 (8.75%) 
Erythema * 1  8/298 (2.68%)  21/297 (7.07%) 
Skin hyperpigmentation * 1  24/298 (8.05%)  20/297 (6.73%) 
Dermatitis * 1  15/298 (5.03%)  14/297 (4.71%) 
Vascular disorders     
Hot flush * 1  31/298 (10.40%)  30/297 (10.10%) 
Hypertension * 1  14/298 (4.70%)  24/297 (8.08%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (19.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00950300     History of Changes
Other Study ID Numbers: BO22227
2008-007326-19 ( EudraCT Number )
First Submitted: July 30, 2009
First Posted: July 31, 2009
Results First Submitted: November 4, 2016
Results First Posted: January 23, 2017
Last Update Posted: January 23, 2018