Trial Outcomes & Findings for Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer (NCT NCT00365365)
NCT ID: NCT00365365
Last Updated: 2012-09-14
Results Overview
Participants were evaluated for clinical CHF every 3 weeks during chemotherapy, every 3 months while on maintenance therapy, and every 3 months during the 2-year follow-up period. Left ventricular ejection fraction (LVEF) of CHF was assessed by multi-gated acquisition (MUGA) or echocardiogram (ECHO) performed midway through completion of chemotherapy according to a treatment-specific schedule, every 12 weeks during maintenance therapy, and at 6 and 24 months after completion of maintenance therapy. Grade 3-4 CHF were identified through a clinical review of all study collected investigator verbatim and the Medical Dictionary for Regulatory Activities (MedDRA). The preferred terms (PT) cardiac failure congestive, cardiomyopathy, and ejection fraction decreased were associated with CHF.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
214 participants
Primary outcome timeframe
from the first dose of study medication up to the end of follow-up (up to 3 yrs)
Results posted on
2012-09-14
Participant Flow
239 participants were screened in this study. 214 were considered eligible for enrollment and 25 were screen failures. Of the 214 eligible participants, 155 were HER2-negative and 59 were HER2-positive.
Participant milestones
| Measure |
Stratum 1 (AC->T + Bevacizumab)
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 2 (TAC + Bevacizumab)
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 3 (TCH + Bevacizumab).)
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
|---|---|---|---|
|
Overall Study
STARTED
|
78
|
77
|
59
|
|
Overall Study
TREATED (SAFETY POPULATION)
|
78
|
75
|
59
|
|
Overall Study
COMPLETED TREATMENT
|
38
|
36
|
45
|
|
Overall Study
COMPLETED
|
44
|
41
|
44
|
|
Overall Study
NOT COMPLETED
|
34
|
36
|
15
|
Reasons for withdrawal
| Measure |
Stratum 1 (AC->T + Bevacizumab)
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 2 (TAC + Bevacizumab)
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 3 (TCH + Bevacizumab).)
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
|---|---|---|---|
|
Overall Study
Randomized but not treated
|
0
|
2
|
0
|
|
Overall Study
Poor compliance to protocol
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
3
|
3
|
3
|
|
Overall Study
Death
|
1
|
3
|
0
|
|
Overall Study
Subject's request
|
11
|
13
|
1
|
|
Overall Study
Disease progression/relapse
|
9
|
6
|
7
|
|
Overall Study
Adverse Event
|
6
|
6
|
3
|
|
Overall Study
Moved
|
2
|
0
|
0
|
|
Overall Study
New cancer
|
1
|
0
|
0
|
|
Overall Study
Withdrew consent
|
1
|
1
|
0
|
|
Overall Study
Second malignancy
|
0
|
1
|
0
|
|
Overall Study
Patient/physician decision
|
0
|
0
|
1
|
Baseline Characteristics
Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer
Baseline characteristics by cohort
| Measure |
Stratum 1 (AC->T + Bevacizumab)
n=78 Participants
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 2 (TAC + Bevacizumab)
n=75 Participants
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 3 (TCH + Bevacizumab).)
n=59 Participants
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Total
n=212 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age Continuous
|
53.0 years
STANDARD_DEVIATION 10.45 • n=5 Participants
|
55.1 years
STANDARD_DEVIATION 9.89 • n=7 Participants
|
50.8 years
STANDARD_DEVIATION 9.61 • n=5 Participants
|
53.1 years
STANDARD_DEVIATION 10.12 • n=4 Participants
|
|
Sex: Female, Male
Female
|
78 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
212 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group Score (ECOG)
ECOG Score = 0
|
73 participants
n=5 Participants
|
67 participants
n=7 Participants
|
55 participants
n=5 Participants
|
195 participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group Score (ECOG)
ECOG Score = 1
|
5 participants
n=5 Participants
|
8 participants
n=7 Participants
|
4 participants
n=5 Participants
|
17 participants
n=4 Participants
|
|
Electrocardiogram (ECG)
Normal
|
45 participants
n=5 Participants
|
53 participants
n=7 Participants
|
36 participants
n=5 Participants
|
134 participants
n=4 Participants
|
|
Electrocardiogram (ECG)
Abnormal
|
22 participants
n=5 Participants
|
19 participants
n=7 Participants
|
19 participants
n=5 Participants
|
60 participants
n=4 Participants
|
|
Electrocardiogram (ECG)
Not done/missing
|
11 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
18 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: from the first dose of study medication up to the end of follow-up (up to 3 yrs)Population: Safety population - participants who received at least one dose of study medication
Participants were evaluated for clinical CHF every 3 weeks during chemotherapy, every 3 months while on maintenance therapy, and every 3 months during the 2-year follow-up period. Left ventricular ejection fraction (LVEF) of CHF was assessed by multi-gated acquisition (MUGA) or echocardiogram (ECHO) performed midway through completion of chemotherapy according to a treatment-specific schedule, every 12 weeks during maintenance therapy, and at 6 and 24 months after completion of maintenance therapy. Grade 3-4 CHF were identified through a clinical review of all study collected investigator verbatim and the Medical Dictionary for Regulatory Activities (MedDRA). The preferred terms (PT) cardiac failure congestive, cardiomyopathy, and ejection fraction decreased were associated with CHF.
Outcome measures
| Measure |
Stratum 1 (AC->T + Bevacizumab)
n=78 Participants
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 2 (TAC + Bevacizumab)
n=75 Participants
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 3 (TCH + Bevacizumab).)
n=59 Participants
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
|---|---|---|---|
|
Cardiac Safety - Number of Participants With Grade 3-4 Clinical Congestive Heart Failure (CHF)
|
1 participants
Interval 0.0 to 6.9
|
3 participants
Interval 0.8 to 11.2
|
1 participants
Interval 0.0 to 0.1
|
SECONDARY outcome
Timeframe: from the administration of the first dose of study medication up to 30 days after the last dose of study medication; events ongoing at the time of discontinuation were monitored in the follow-up period until resolution.Population: Safety population - participants who received at least one dose of study medication
An adverse event was any untoward medical occurrence in a participant of the clinical investigation, regardless of the relationship to study treatment. A serious adverse event (SAE) was an AE that at any dose (including overdose) resulted in death, was life-threatening, required inpatient hospitalization or prolonged existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect, and/or was medically important. Treatment-emergent adverse events (TEAE) were defined as AEs that developed or worsened in severity during the on-treatment period.
Outcome measures
| Measure |
Stratum 1 (AC->T + Bevacizumab)
n=78 Participants
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 2 (TAC + Bevacizumab)
n=75 Participants
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 3 (TCH + Bevacizumab).)
n=59 Participants
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
|---|---|---|---|
|
Safety - Number of Participants With Adverse Events (AE)
with TEAE
|
78 participants
|
75 participants
|
59 participants
|
|
Safety - Number of Participants With Adverse Events (AE)
with serious TEAE
|
23 participants
|
24 participants
|
12 participants
|
|
Safety - Number of Participants With Adverse Events (AE)
with any TEAE leading to death
|
0 participants
|
2 participants
|
0 participants
|
|
Safety - Number of Participants With Adverse Events (AE)
with any TEAE leading to treatment discontinuation
|
21 participants
|
24 participants
|
16 participants
|
|
Safety - Number of Participants With Adverse Events (AE)
with any Grade 3-4 Serious TEAE
|
23 participants
|
24 participants
|
9 participants
|
SECONDARY outcome
Timeframe: from the administration of the first-dose of study medication up to 12 months, 18 months and 24 monthsPopulation: Intent-to-treat population - All randomized participants
DFS was defined as the time from the administration of the first-dose of study medication until recurrence of tumor or death from any cause in the absence of previous documentation of tumor recurrence. DFS rate was the probability of being disease free and alive at a particular time. DFS rates were estimated using Kaplan-Meier Method, and 95% confidence intervals were computed using the method of Kalbfleisch and Prentice. For participants who did have objective recurrence of tumor and who were still on study at the time of an analysis, or who were given antitumor treatment other than the study treatment, or who were removed from study follow-up prior to documentation of the tumor recurrence, DFS was censored at the last date the participant was known to be disease-free.
Outcome measures
| Measure |
Stratum 1 (AC->T + Bevacizumab)
n=10 Number of DFS events
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 2 (TAC + Bevacizumab)
n=9 Number of DFS events
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
Stratum 3 (TCH + Bevacizumab).)
n=7 Number of DFS events
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
|---|---|---|---|
|
Disease-free Survival (DFS) Rate
DFS rate at 12 months
|
93.6 percentage of participants
Interval 83.8 to 97.5
|
95.9 percentage of participants
Interval 87.8 to 98.7
|
98.2 percentage of participants
Interval 87.8 to 99.7
|
|
Disease-free Survival (DFS) Rate
DFS rate at 24 months
|
87.1 percentage of participants
Interval 75.9 to 93.4
|
94.1 percentage of participants
Interval 84.8 to 97.8
|
96.3 percentage of participants
Interval 86.0 to 99.1
|
|
Disease-free Survival (DFS) Rate
DFS rate at 36 months
|
85.5 percentage of participants
Interval 74.0 to 92.2
|
90.4 percentage of participants
Interval 79.6 to 95.6
|
90.4 percentage of participants
Interval 78.5 to 95.9
|
Adverse Events
AC->T + Bevacizumab
Serious events: 23 serious events
Other events: 78 other events
Deaths: 0 deaths
TAC + Bevacizumab
Serious events: 24 serious events
Other events: 75 other events
Deaths: 0 deaths
TCH + Bevacizumab
Serious events: 12 serious events
Other events: 59 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AC->T + Bevacizumab
n=78 participants at risk
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
TAC + Bevacizumab
n=75 participants at risk
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
TCH + Bevacizumab
n=59 participants at risk
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.1%
4/78
|
10.7%
8/75
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.3%
1/78
|
4.0%
3/75
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/78
|
2.7%
2/75
|
0.00%
0/59
|
|
Cardiac disorders
Acute coronary syndrome
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Cardiac disorders
Cardiac failure congestive
|
1.3%
1/78
|
2.7%
2/75
|
0.00%
0/59
|
|
Cardiac disorders
Myocardial infarction
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal pain
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Gastrointestinal disorders
Diarrhoea
|
1.3%
1/78
|
1.3%
1/75
|
1.7%
1/59
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Gastrointestinal disorders
Caecitis
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/78
|
2.7%
2/75
|
0.00%
0/59
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Gastrointestinal disorders
Intestinal ulcer
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Gastrointestinal disorders
Oesophagitis ulcerative
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
General disorders
Mucosal inflammation
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
General disorders
Chest pain
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/78
|
1.3%
1/75
|
1.7%
1/59
|
|
General disorders
Pyrexia
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Appendicitis
|
1.3%
1/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Bronchitis
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Infections and infestations
Diverticulitis
|
1.3%
1/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Hand-foot-and-mouth disease
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Infections and infestations
Influenza
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Infections and infestations
Neutropenic infection
|
1.3%
1/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Device related infection
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Incision site abscess
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Infections and infestations
Lung infection pseudomonal
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Pseudomonal sepsis
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Sepsis
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Septic shock
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/78
|
5.3%
4/75
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Nervous system disorders
Headache
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Nervous system disorders
Lacunar infarction
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Nervous system disorders
Neuropathy peripheral
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Reproductive system and breast disorders
Female genital tract fistula
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.3%
1/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
1.3%
1/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Vascular disorders
Deep vein thrombosis
|
2.6%
2/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Vascular disorders
Hypertension
|
1.3%
1/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Vascular disorders
Hypotension
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
|
Vascular disorders
Superior vena cava syndrome
|
0.00%
0/78
|
1.3%
1/75
|
0.00%
0/59
|
Other adverse events
| Measure |
AC->T + Bevacizumab
n=78 participants at risk
HER2-negative participants administered
* doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
* docetaxel (T) + bevacizumab for 4 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
TAC + Bevacizumab
n=75 participants at risk
HER2-negative participants administered
* docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
* bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
TCH + Bevacizumab
n=59 participants at risk
All HER2-positive participants administered
* docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
* bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
|
|---|---|---|---|
|
Gastrointestinal disorders
Stomatitis
|
24.4%
19/78
|
22.7%
17/75
|
11.9%
7/59
|
|
Gastrointestinal disorders
Dysphagia
|
15.4%
12/78
|
12.0%
9/75
|
6.8%
4/59
|
|
Gastrointestinal disorders
Dry mouth
|
14.1%
11/78
|
6.7%
5/75
|
5.1%
3/59
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
12.8%
10/78
|
13.3%
10/75
|
6.8%
4/59
|
|
Gastrointestinal disorders
Abdominal pain
|
10.3%
8/78
|
24.0%
18/75
|
20.3%
12/59
|
|
Gastrointestinal disorders
Oesophagitis
|
10.3%
8/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Gastrointestinal disorders
Oral pain
|
10.3%
8/78
|
10.7%
8/75
|
15.3%
9/59
|
|
Gastrointestinal disorders
Gingival bleeding
|
7.7%
6/78
|
9.3%
7/75
|
5.1%
3/59
|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.4%
5/78
|
4.0%
3/75
|
3.4%
2/59
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.4%
5/78
|
5.3%
4/75
|
8.5%
5/59
|
|
Gastrointestinal disorders
Haemorrhoids
|
6.4%
5/78
|
2.7%
2/75
|
8.5%
5/59
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
6.4%
5/78
|
4.0%
3/75
|
11.9%
7/59
|
|
Blood and lymphatic system disorders
Anaemia
|
57.7%
45/78
|
56.0%
42/75
|
54.2%
32/59
|
|
Blood and lymphatic system disorders
Neutropenia
|
52.6%
41/78
|
54.7%
41/75
|
13.6%
8/59
|
|
Blood and lymphatic system disorders
Leukopenia
|
42.3%
33/78
|
46.7%
35/75
|
22.0%
13/59
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
33.3%
26/78
|
49.3%
37/75
|
49.2%
29/59
|
|
Blood and lymphatic system disorders
Lymphopenia
|
10.3%
8/78
|
10.7%
8/75
|
5.1%
3/59
|
|
Blood and lymphatic system disorders
Leukocytosis
|
5.1%
4/78
|
8.0%
6/75
|
1.7%
1/59
|
|
Blood and lymphatic system disorders
Granulocytosis
|
3.8%
3/78
|
4.0%
3/75
|
5.1%
3/59
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.6%
2/78
|
10.7%
8/75
|
0.00%
0/59
|
|
Cardiac disorders
Tachycardia
|
5.1%
4/78
|
16.0%
12/75
|
5.1%
3/59
|
|
Ear and labyrinth disorders
Ear pain
|
7.7%
6/78
|
4.0%
3/75
|
3.4%
2/59
|
|
Ear and labyrinth disorders
Vertigo
|
1.3%
1/78
|
0.00%
0/75
|
5.1%
3/59
|
|
Eye disorders
Lacrimation increased
|
37.2%
29/78
|
10.7%
8/75
|
28.8%
17/59
|
|
Eye disorders
Vision blurred
|
7.7%
6/78
|
1.3%
1/75
|
5.1%
3/59
|
|
Eye disorders
Visual impairment
|
5.1%
4/78
|
2.7%
2/75
|
1.7%
1/59
|
|
Eye disorders
Blepharospasm
|
0.00%
0/78
|
5.3%
4/75
|
5.1%
3/59
|
|
Gastrointestinal disorders
Nausea
|
82.1%
64/78
|
80.0%
60/75
|
86.4%
51/59
|
|
Gastrointestinal disorders
Constipation
|
51.3%
40/78
|
38.7%
29/75
|
50.8%
30/59
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
39/78
|
64.0%
48/75
|
64.4%
38/59
|
|
Gastrointestinal disorders
Vomiting
|
41.0%
32/78
|
41.3%
31/75
|
39.0%
23/59
|
|
Gastrointestinal disorders
Dyspepsia
|
25.6%
20/78
|
21.3%
16/75
|
20.3%
12/59
|
|
Gastrointestinal disorders
Abdominal distension
|
5.1%
4/78
|
5.3%
4/75
|
6.8%
4/59
|
|
Gastrointestinal disorders
Haematochezia
|
3.8%
3/78
|
2.7%
2/75
|
8.5%
5/59
|
|
Gastrointestinal disorders
Mouth ulceration
|
3.8%
3/78
|
4.0%
3/75
|
10.2%
6/59
|
|
General disorders
Fatigue
|
91.0%
71/78
|
81.3%
61/75
|
86.4%
51/59
|
|
General disorders
Mucosal inflammation
|
47.4%
37/78
|
21.3%
16/75
|
25.4%
15/59
|
|
General disorders
Pyrexia
|
26.9%
21/78
|
32.0%
24/75
|
25.4%
15/59
|
|
General disorders
Oedema peripheral
|
20.5%
16/78
|
14.7%
11/75
|
11.9%
7/59
|
|
General disorders
Asthenia
|
19.2%
15/78
|
26.7%
20/75
|
18.6%
11/59
|
|
General disorders
Pain
|
16.7%
13/78
|
6.7%
5/75
|
10.2%
6/59
|
|
General disorders
Chills
|
12.8%
10/78
|
6.7%
5/75
|
11.9%
7/59
|
|
General disorders
Oedema
|
7.7%
6/78
|
5.3%
4/75
|
10.2%
6/59
|
|
General disorders
Catheter site pain
|
5.1%
4/78
|
6.7%
5/75
|
6.8%
4/59
|
|
General disorders
Influenza like illness
|
5.1%
4/78
|
2.7%
2/75
|
5.1%
3/59
|
|
General disorders
Tenderness
|
3.8%
3/78
|
1.3%
1/75
|
5.1%
3/59
|
|
General disorders
Chest discomfort
|
2.6%
2/78
|
2.7%
2/75
|
11.9%
7/59
|
|
Immune system disorders
Seasonal allergy
|
5.1%
4/78
|
2.7%
2/75
|
5.1%
3/59
|
|
Infections and infestations
Candidiasis
|
15.4%
12/78
|
5.3%
4/75
|
1.7%
1/59
|
|
Infections and infestations
Sinusitis
|
10.3%
8/78
|
12.0%
9/75
|
16.9%
10/59
|
|
Infections and infestations
Nasopharyngitis
|
9.0%
7/78
|
9.3%
7/75
|
13.6%
8/59
|
|
Infections and infestations
Upper respiratory tract infection
|
9.0%
7/78
|
9.3%
7/75
|
11.9%
7/59
|
|
Infections and infestations
Urinary tract infection
|
9.0%
7/78
|
18.7%
14/75
|
16.9%
10/59
|
|
Infections and infestations
Oral candidiasis
|
7.7%
6/78
|
0.00%
0/75
|
0.00%
0/59
|
|
Infections and infestations
Cellulitis
|
6.4%
5/78
|
2.7%
2/75
|
0.00%
0/59
|
|
Infections and infestations
Catheter site infection
|
2.6%
2/78
|
0.00%
0/75
|
5.1%
3/59
|
|
Infections and infestations
Pharyngitis
|
2.6%
2/78
|
2.7%
2/75
|
5.1%
3/59
|
|
Infections and infestations
Bronchitis
|
1.3%
1/78
|
6.7%
5/75
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
15.4%
12/78
|
12.0%
9/75
|
15.3%
9/59
|
|
Injury, poisoning and procedural complications
Contusion
|
2.6%
2/78
|
2.7%
2/75
|
6.8%
4/59
|
|
Investigations
Weight decreased
|
11.5%
9/78
|
13.3%
10/75
|
8.5%
5/59
|
|
Investigations
Aspartate aminotransferase increased
|
10.3%
8/78
|
4.0%
3/75
|
11.9%
7/59
|
|
Investigations
Alanine aminotransferase increased
|
9.0%
7/78
|
4.0%
3/75
|
11.9%
7/59
|
|
Investigations
Ejection fraction decreased
|
6.4%
5/78
|
9.3%
7/75
|
11.9%
7/59
|
|
Investigations
Blood pressure increased
|
5.1%
4/78
|
6.7%
5/75
|
0.00%
0/59
|
|
Investigations
Blood alkaline phosphatase increased
|
3.8%
3/78
|
0.00%
0/75
|
10.2%
6/59
|
|
Investigations
Haemoglobin decreased
|
3.8%
3/78
|
1.3%
1/75
|
8.5%
5/59
|
|
Investigations
Platelet count decreased
|
2.6%
2/78
|
4.0%
3/75
|
6.8%
4/59
|
|
Investigations
Blood glucose increased
|
1.3%
1/78
|
6.7%
5/75
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Decreased appetite
|
50.0%
39/78
|
33.3%
25/75
|
37.3%
22/59
|
|
Metabolism and nutrition disorders
Dehydration
|
25.6%
20/78
|
22.7%
17/75
|
10.2%
6/59
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
11.5%
9/78
|
12.0%
9/75
|
8.5%
5/59
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
5.1%
4/78
|
2.7%
2/75
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/78
|
1.3%
1/75
|
5.1%
3/59
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
65.4%
51/78
|
49.3%
37/75
|
54.2%
32/59
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
48.7%
38/78
|
30.7%
23/75
|
35.6%
21/59
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
28.2%
22/78
|
30.7%
23/75
|
40.7%
24/59
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
28.2%
22/78
|
20.0%
15/75
|
25.4%
15/59
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
23.1%
18/78
|
21.3%
16/75
|
16.9%
10/59
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
14.1%
11/78
|
9.3%
7/75
|
6.8%
4/59
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
14.1%
11/78
|
2.7%
2/75
|
5.1%
3/59
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
9.0%
7/78
|
5.3%
4/75
|
10.2%
6/59
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
3.8%
3/78
|
6.7%
5/75
|
6.8%
4/59
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
1.3%
1/78
|
6.7%
5/75
|
1.7%
1/59
|
|
Nervous system disorders
Headache
|
47.4%
37/78
|
34.7%
26/75
|
40.7%
24/59
|
|
Nervous system disorders
Neuropathy peripheral
|
25.6%
20/78
|
10.7%
8/75
|
20.3%
12/59
|
|
Nervous system disorders
Dysgeusia
|
23.1%
18/78
|
25.3%
19/75
|
30.5%
18/59
|
|
Nervous system disorders
Dizziness
|
16.7%
13/78
|
16.0%
12/75
|
13.6%
8/59
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
15.4%
12/78
|
9.3%
7/75
|
8.5%
5/59
|
|
Nervous system disorders
Hypoaesthesia
|
9.0%
7/78
|
5.3%
4/75
|
8.5%
5/59
|
|
Nervous system disorders
Sinus headache
|
9.0%
7/78
|
2.7%
2/75
|
1.7%
1/59
|
|
Nervous system disorders
Paraesthesia
|
6.4%
5/78
|
8.0%
6/75
|
10.2%
6/59
|
|
Nervous system disorders
Migraine
|
3.8%
3/78
|
2.7%
2/75
|
5.1%
3/59
|
|
Psychiatric disorders
Insomnia
|
38.5%
30/78
|
40.0%
30/75
|
27.1%
16/59
|
|
Psychiatric disorders
Anxiety
|
20.5%
16/78
|
17.3%
13/75
|
15.3%
9/59
|
|
Psychiatric disorders
Depression
|
12.8%
10/78
|
13.3%
10/75
|
18.6%
11/59
|
|
Renal and urinary disorders
Proteinuria
|
17.9%
14/78
|
16.0%
12/75
|
18.6%
11/59
|
|
Renal and urinary disorders
Dysuria
|
7.7%
6/78
|
4.0%
3/75
|
3.4%
2/59
|
|
Renal and urinary disorders
Haematuria
|
2.6%
2/78
|
8.0%
6/75
|
5.1%
3/59
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
5.1%
4/78
|
1.3%
1/75
|
5.1%
3/59
|
|
Reproductive system and breast disorders
Breast pain
|
2.6%
2/78
|
8.0%
6/75
|
11.9%
7/59
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
46.2%
36/78
|
42.7%
32/75
|
54.2%
32/59
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
41.0%
32/78
|
28.0%
21/75
|
28.8%
17/59
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.8%
17/78
|
20.0%
15/75
|
20.3%
12/59
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.9%
14/78
|
24.0%
18/75
|
22.0%
13/59
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
16.7%
13/78
|
18.7%
14/75
|
20.3%
12/59
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
10.3%
8/78
|
5.3%
4/75
|
10.2%
6/59
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.7%
6/78
|
5.3%
4/75
|
6.8%
4/59
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.1%
4/78
|
6.7%
5/75
|
3.4%
2/59
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
5.1%
4/78
|
6.7%
5/75
|
8.5%
5/59
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
1.3%
1/78
|
1.3%
1/75
|
5.1%
3/59
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
74.4%
58/78
|
64.0%
48/75
|
84.7%
50/59
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
29.5%
23/78
|
4.0%
3/75
|
18.6%
11/59
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
24.4%
19/78
|
0.00%
0/75
|
3.4%
2/59
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.5%
16/78
|
13.3%
10/75
|
33.9%
20/59
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
7.7%
6/78
|
6.7%
5/75
|
11.9%
7/59
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.4%
5/78
|
0.00%
0/75
|
3.4%
2/59
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.1%
4/78
|
8.0%
6/75
|
6.8%
4/59
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.1%
4/78
|
5.3%
4/75
|
10.2%
6/59
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
5.1%
4/78
|
0.00%
0/75
|
1.7%
1/59
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.8%
3/78
|
12.0%
9/75
|
11.9%
7/59
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/78
|
1.3%
1/75
|
5.1%
3/59
|
|
Surgical and medical procedures
Sinus operation
|
11.5%
9/78
|
8.0%
6/75
|
8.5%
5/59
|
|
Vascular disorders
Hot flush
|
32.1%
25/78
|
24.0%
18/75
|
20.3%
12/59
|
|
Vascular disorders
Hypertension
|
29.5%
23/78
|
28.0%
21/75
|
27.1%
16/59
|
|
Vascular disorders
Lymphoedema
|
15.4%
12/78
|
10.7%
8/75
|
8.5%
5/59
|
|
Vascular disorders
Flushing
|
2.6%
2/78
|
6.7%
5/75
|
8.5%
5/59
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 days for abstracts) in advance of any submission for publication. The Sponsor may request for the publication to be delayed for upto 90 days to preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER