Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) Plus Herceptin (Trastuzumab) in Patients With Primary Inflammatory HER2-Positive Breast Cancer. (NCT NCT00717405)
NCT ID: NCT00717405
Last Updated: 2016-08-02
Results Overview
PCR was assessed at the time of definitive surgery according to Sataloff classification and centrally reviewed by an independent committee under blinded conditions. Pathological response was defined based on the therapeutic response at the primary tumor site and axillary lymph nodes. Primary tumor response criteria were as follows: T-A (Total / near total therapeutic effect), T-B (Subjectively greater than \[\>\] 50 percent \[%\] therapeutic effect but less than \[\<\] T-A), T-C (\<50% therapeutic effect, but effect evident), T-D (No therapeutic effect). Axillary lymph node response: N-A (Evidence of therapeutic effect, no metastases), N-B (No therapeutic effect, no nodal metastases), N-C (Nodal metastasis but evident therapeutic effect), N-D (Nodal metastasis with no therapeutic effect). T-A and N-A or T-A and N-B responses were defined as PCR and all other tumor responses as non-responders. Participants with missing values were considered as non-responders.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
From baseline through Week 25 (Up to 6 months)
Results posted on
2016-08-02
Participant Flow
Participant milestones
| Measure |
Bevacizumab + Trastuzumab Chemotherapy
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 milligrams per kilogram (mg/kg) intravenous (IV) bevacizumab every 3 weeks (q3w) for 8 cycles, 4 cycles of 500 milligrams per squared-meter (mg/m\^2) IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Overall Study
STARTED
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52
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Overall Study
COMPLETED
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52
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Avastin (Bevacizumab) Plus Herceptin (Trastuzumab) in Patients With Primary Inflammatory HER2-Positive Breast Cancer.
Baseline characteristics by cohort
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Age, Continuous
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51.48 years
STANDARD_DEVIATION 9.78 • n=5 Participants
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Sex: Female, Male
Female
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52 Participants
n=5 Participants
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Sex: Female, Male
Male
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0 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: From baseline through Week 25 (Up to 6 months)Population: ITT population.
PCR was assessed at the time of definitive surgery according to Sataloff classification and centrally reviewed by an independent committee under blinded conditions. Pathological response was defined based on the therapeutic response at the primary tumor site and axillary lymph nodes. Primary tumor response criteria were as follows: T-A (Total / near total therapeutic effect), T-B (Subjectively greater than \[\>\] 50 percent \[%\] therapeutic effect but less than \[\<\] T-A), T-C (\<50% therapeutic effect, but effect evident), T-D (No therapeutic effect). Axillary lymph node response: N-A (Evidence of therapeutic effect, no metastases), N-B (No therapeutic effect, no nodal metastases), N-C (Nodal metastasis but evident therapeutic effect), N-D (Nodal metastasis with no therapeutic effect). T-A and N-A or T-A and N-B responses were defined as PCR and all other tumor responses as non-responders. Participants with missing values were considered as non-responders.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants With a Pathological Complete Response (PCR) According to the Sataloff Classification
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63.46 percentage of participants
Interval 49.41 to 77.51
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SECONDARY outcome
Timeframe: From baseline through Week 25 (Up to 6 months)Population: ITT population.
PCR was assessed at the time of definitive surgery according to Chevallier classification and centrally reviewed by an independent committee under blinded conditions. The Chevallier classification for grading of therapeutic effect related to the primary tumor site and axillary lymph nodes was defined by microscopic changes as follows - Grade 1: Disappearance of all tumors either in the breast or in the nodes, Grade 2: Persistence of carcinoma in situ in the breast only and no nodal invasion, Grade 3: Presence of invasive carcinoma with stromal alteration, Grade 4: Presence of invasive carcinoma without modification. Grade 1 response was considered as PCR. Participants with missing values were considered as non-responders.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants With a PCR According to the Chevallier Classification
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53.85 percentage of participants
Interval 39.34 to 68.36
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SECONDARY outcome
Timeframe: Baseline, Cycle 5 (Week 15), Neo-adjuvant treatment final visit (Week 25)Population: ITT population. Number of participants analyzed included participants for whom tumor physical examination was performed and were evaluated for response from baseline assessment of inflammatory signs. n included number of participants who were evaluable at a particular time point.
Breast tumor was physically evaluated during the study which included assessment for inflammatory signs and for overall clinical response. Participant with response from baseline based on inflammatory signs at Cycle 5 and final treatment visit were presented.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=43 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants Who Were Responders Based on Inflammatory Signs From Baseline at Cycle 5 and Final Treatment Visit
Response from baseline at Week 15 (n=43)
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88.4 percentage of participants
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Percentage of Participants Who Were Responders Based on Inflammatory Signs From Baseline at Cycle 5 and Final Treatment Visit
Response from baseline at Week 25 (n=42)
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100.0 percentage of participants
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SECONDARY outcome
Timeframe: Baseline, Cycle 5 (Week 15), Neo-adjuvant treatment final visit (Week 25)Population: ITT population. Number of participants analyzed included participants for whom tumor physical examination was performed. n included number of participants who were evaluable at a particular time point.
Breast tumor was physically evaluated during the study which included assessment for inflammatory signs and for overall clinical response. Participant with response from baseline based on overall clinical response at Cycle 5 and final treatment visit were presented.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=45 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants Who Were Responders Based on Overall Clinical Response From Baseline at Cycle 5 and Final Treatment Visit
Response from baseline at Week 15 (n=44)
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90.9 percentage of participants
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Percentage of Participants Who Were Responders Based on Overall Clinical Response From Baseline at Cycle 5 and Final Treatment Visit
Response from baseline at Week 25 (n=45)
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97.8 percentage of participants
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SECONDARY outcome
Timeframe: Anytime between Week 26 and Week 29Population: ITT population.
Surgery included a mastectomy with axillary node dissection and had to be performed at least 4 weeks after the last infusion of neoadjuvant bevacizumab treatment.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Number of Participants Who Underwent Mastectomy
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49 participants
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SECONDARY outcome
Timeframe: Anytime between Week 26 and Week 29Population: ITT population. Included participants who underwent mastectomy.
Local pathologists assessed the tumor whether it was macroscopically visible or not and percentage of participants for whom the tumor was macroscopically visible was reported.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=49 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants With Macroscopically Visible Tumor
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26.5 percentage of participants
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SECONDARY outcome
Timeframe: Anytime between Week 26 and Week 29Population: ITT population. Included participants who underwent mastectomy.
Among the participants who were planned to undergo mastectomy, lymph node resection was also performed by the physician depending up on the participant's breast cancer grades.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=49 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants Who Underwent Lymph Node Resection
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98.0 percentage of participants
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SECONDARY outcome
Timeframe: Baseline, Neoadjuvant Final Visit (Week 25)Population: Safety population: Number of participants included all the participants who received at least one infusion of bevacizumab. n included participants who were evaluable at that time point.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Breast Cancer Marker CA15.3 at Baseline, Neoadjuvant Final Visit and Change From Baseline at Neoadjuvant Final Visit
Baseline (n=52)
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39.66 Units per milliliter (U/mL)
Standard Deviation 79.49
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Breast Cancer Marker CA15.3 at Baseline, Neoadjuvant Final Visit and Change From Baseline at Neoadjuvant Final Visit
Neoadjuvant final visit (n=37)
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29.39 Units per milliliter (U/mL)
Standard Deviation 10.06
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Breast Cancer Marker CA15.3 at Baseline, Neoadjuvant Final Visit and Change From Baseline at Neoadjuvant Final Visit
Change in CA15.3 at neoadjuvant final visit (n=37)
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-3.39 Units per milliliter (U/mL)
Standard Deviation 33.05
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SECONDARY outcome
Timeframe: 3, 5 yearsPopulation: ITT population.
A participant was considered disease free if the participant did not experience any of the following events: local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants Who Were Disease Free at 3 and 5 Years
3 years
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66.7 percentage of participants
Interval 52.0 to 77.8
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Percentage of Participants Who Were Disease Free at 3 and 5 Years
5 years
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60.8 percentage of participants
Interval 46.1 to 72.7
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SECONDARY outcome
Timeframe: Up to 5 YearsPopulation: ITT population.
DFS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Disease Free Survival (DFS) Duration
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NA months
Using Kaplan-Meier method, median DFS was not reached due to higher (\>50%) number of censored participants.
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SECONDARY outcome
Timeframe: 3, 5 yearsPopulation: ITT population.
A participant was considered recurrence free if the participant did not experience local or regional recurrence (wall or axillaries nodes), or occurrence of distant metastases (including soft tissue and distal lymph nodes).
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants Who Were Recurrence Free at 3 and 5 Years
3 years
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69.7 percentage of participants
Interval 54.8 to 80.5
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Percentage of Participants Who Were Recurrence Free at 3 and 5 Years
5 years
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65.4 percentage of participants
Interval 50.4 to 76.9
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SECONDARY outcome
Timeframe: Up to 5 YearsPopulation: ITT population.
RFS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Recurrence Free Survival (RFS) Duration
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NA months
Using Kaplan-Meier method, median RFS was not reached due to higher (\>50%) number of censored participants.
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SECONDARY outcome
Timeframe: 3, 5 yearsPopulation: ITT population.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Percentage of Participants Who Were Alive at 3 and 5 Years
Alive at 3 years
|
90.0 percentage of participants
Interval 77.6 to 95.7
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Percentage of Participants Who Were Alive at 3 and 5 Years
Alive at 5 years
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81.8 percentage of participants
Interval 67.9 to 90.1
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SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: ITT population.
OS was defined as the time from the first administration of neoadjuvant treatment to death of any cause. OS was estimated using Kaplan-Meier method.
Outcome measures
| Measure |
Bevacizumab + Trastuzumab
n=52 Participants
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Overall Survival (OS) Duration
|
NA months
Using Kaplan-Meier method, Median OS was not reached due to higher (\>50%) number of censored participants
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Adverse Events
Bevacizumab + Trastuzumab
Serious events: 20 serious events
Other events: 52 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab + Trastuzumab
n=52 participants at risk
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
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Blood and lymphatic system disorders
Febrile bone marrow aplasia
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
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Blood and lymphatic system disorders
Febrile neutropenia
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Vomiting
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Hyperthermia
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
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General disorders
Malaise
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Pyrexia
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Anal abscess
|
3.8%
2/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Appendicitis
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Septic shock
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Investigations
Ejection fraction decreased
|
3.8%
2/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
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Reproductive system and breast disorders
Metrorrhagia
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Vascular disorders
Jugular vein thrombosis
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Blood and lymphatic system disorders
Leukopenia
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Cardiac disorders
Atrial tachycardia
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Tooth loss
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Impaired healing
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Inflammation
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Incision site abscess
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Pyelonephritis
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum perforation
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Vascular disorders
Hypertension
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Vascular disorders
Lymphocele
|
1.9%
1/52 • From Baseline until end of study (Up to approximately 6 years)
|
Other adverse events
| Measure |
Bevacizumab + Trastuzumab
n=52 participants at risk
Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
21.2%
11/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Blood and lymphatic system disorders
Leukopenia
|
13.5%
7/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Blood and lymphatic system disorders
Neutropenia
|
46.2%
24/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Cardiac disorders
Cardiac failure congestive
|
19.2%
10/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Eye disorders
Conjunctivitis
|
23.1%
12/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Eye disorders
Lacrimation increased
|
25.0%
13/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Abdominal pain
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
21.2%
11/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Constipation
|
26.9%
14/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Diarrhoea
|
17.3%
9/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Dyspepsia
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Dysphagia
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Gingival bleeding
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Gingivitis
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Haemorrhoids
|
13.5%
7/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Nausea
|
69.2%
36/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Vomiting
|
34.6%
18/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Asthenia
|
78.8%
41/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Fatigue
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Mucosal inflammation
|
65.4%
34/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Oedema peripheral
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Pyrexia
|
19.2%
10/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Bronchitis
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Nasopharyngitis
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Oral fungal infection
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Pharyngitis
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Rhinitis
|
17.3%
9/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Tonsillitis
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Tooth abscess
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Urinary tract infection
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
36.5%
19/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Investigations
Weight decreased
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Metabolism and nutrition disorders
Anorexia
|
23.1%
12/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
28.8%
15/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
25.0%
13/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Nervous system disorders
Ageusia
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Nervous system disorders
Dysgeusia
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Nervous system disorders
Headache
|
32.7%
17/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Nervous system disorders
Neuropathy peripheral
|
19.2%
10/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Psychiatric disorders
Anxiety
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Psychiatric disorders
Insomnia
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Renal and urinary disorders
Proteinuria
|
61.5%
32/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Reproductive system and breast disorders
Breast pain
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.4%
8/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
63.5%
33/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
13.5%
7/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
69.2%
36/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
17.3%
9/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
30.8%
16/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Nail toxicity
|
13.5%
7/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Onycholysis
|
19.2%
10/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
17.3%
9/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Skin toxicity
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Vascular disorders
Hypertension
|
40.4%
21/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Ear and labyrinth disorders
Vertigo
|
11.5%
6/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Oesophagitis
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Chest pain
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
General disorders
Pain
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Vascular disorders
Hot flush
|
13.5%
7/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Vascular disorders
Lymphocele
|
28.8%
15/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Vascular disorders
Lymphoedema
|
19.2%
10/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Cystitis
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Sinusitis
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Skin infection
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Infections and infestations
Tooth infection
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Investigations
Ejection fraction decreased
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Nervous system disorders
Neuralgia
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Nervous system disorders
Paraesthesia
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
9.6%
5/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
7.7%
4/52 • From Baseline until end of study (Up to approximately 6 years)
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
5.8%
3/52 • From Baseline until end of study (Up to approximately 6 years)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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