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Study To Evaluate the Efficacy and Safety Of Bevacizumab, and Associated Biomarkers, In Combination With Paclitaxel Compared With Paclitaxel Plus Placebo as First-line Treatment Of Patients With Her2-Negative Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT01663727
Recruitment Status : Completed
First Posted : August 13, 2012
Results First Posted : February 10, 2016
Last Update Posted : January 21, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Interventions Drug: Bevacizumab [Avastin]
Drug: Paclitaxel
Drug: Placebo
Enrollment 481
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death. Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Period Title: Overall Study
Started 242 239
Completed 0 1
Not Completed 242 238
Reason Not Completed
Death             161             155
Lost to Follow-up             10             8
Withdrawal by Subject             18             25
Study Terminated             51             50
Withdrawal by subject and Adverse Event.             1             0
Withdrawal prior to dosing.             1             0
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab Total
Hide Arm/Group Description Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death. Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death. Total of all reporting groups
Overall Number of Baseline Participants 242 239 481
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population: All participants randomized to study treatment irrespective of whether the assigned treatment was actually received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 242 participants 239 participants 481 participants
54.7  (10.7) 55.8  (11.5) 55.3  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 239 participants 481 participants
Female
237
  97.9%
236
  98.7%
473
  98.3%
Male
5
   2.1%
3
   1.3%
8
   1.7%
1.Primary Outcome
Title Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population
Hide Description Tumor assessment was performed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator. Disease progression was defined as at least 20 percent (%) increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm), unequivocal progression of existing non-target lesions, or presence of new lesions.
Time Frame Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 242 239
Measure Type: Number
Unit of Measure: percentage of participants
69.4 63.6
2.Primary Outcome
Title Progression Free Survival (PFS) in ITT Population
Hide Description PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
Time Frame Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 242 239
Median (95% Confidence Interval)
Unit of Measure: months
8.8
(7.4 to 9.3)
11.0
(9.5 to 12.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Stratified analysis: Stratification factors were plasma VEGF-A level (low/high), prior adjuvant chemotherapy (yes/no) and estrogen receptor / progesterone receptor status (positive, negative).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 99%
0.51 to 0.91
Estimation Comments Hazards ratio was estimated by Cox regression.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Unstratified Analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 99%
0.55 to 0.97
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments A stratified multivariate Cox regression model, including treatment, VEGF-A level, and interaction between treatment and VEGF-A level (low, high) as factors was used to estimate the interaction p-value of the treatment with VEGF-A level for PFS. Analysis for the interaction of treatment effect with the plasma VEGF-A levels was a secondary objective.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4619
Comments [Not Specified]
Method Wald Test
Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants With Progression or Death in High Baseline Plasma Vascular Endothelial Growth Factor-A (VEGF-A) ITT Population
Hide Description Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions.
Time Frame Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
High baseline plasma VEGF-A ITT population: All participants randomized to study treatment with high baseline plasma VEGF-A levels (VEGF-A levels greater than or equal to 5.05 picograms per milliliter), irrespective of whether the assigned treatment was actually received.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 124 120
Measure Type: Number
Unit of Measure: percentage of participants
75.0 70.8
4.Primary Outcome
Title PFS in High Baseline Plasma VEGF-A ITT Population
Hide Description PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
Time Frame Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
High baseline plasma VEGF-A ITT population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 124 120
Median (95% Confidence Interval)
Unit of Measure: months
7.3
(5.6 to 8.7)
9.6
(9.0 to 11.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Stratified analysis: Stratification factors were prior adjuvant chemotherapy (yes/no) and estrogen receptor / progesterone receptor status (positive, negative).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0038
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 96%
0.47 to 0.88
Estimation Comments Hazards ratio was estimated by Cox regression.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Unstratified analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0101
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 96%
0.50 to 0.93
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Who Died - ITT Population
Hide Description [Not Specified]
Time Frame From randomization till death or clinical cut-off (up to 244 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 242 239
Measure Type: Number
Unit of Measure: percentage of participants
64.9 64.0
6.Secondary Outcome
Title Overall Survival (OS) - ITT Population
Hide Description OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.
Time Frame From randomization till death or clinical cut-off (up to 244 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 242 239
Median (95% Confidence Interval)
Unit of Measure: months
25.8
(21.8 to 30.2)
28.8
(22.8 to 32.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Stratified analysis: Stratified analysis: Stratification factors were plasma VEGF-A level (low/high), prior adjuvant chemotherapy (yes/no) and estrogen receptor / progesterone receptor status (positive, negative).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5877
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%
0.75 to 1.18
Estimation Comments Hazards ratio was estimated by Cox regression.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Unstratified analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8004
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.78 to 1.21
Estimation Comments Hazards ratio was estimated by Cox regression.
7.Secondary Outcome
Title Percentage of Participants Who Died - High Baseline Plasma VEGF-A ITT Population
Hide Description [Not Specified]
Time Frame From randomization till death or clinical cut-off (up to 244 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
High Baseline Plasma VEGF-A ITT Population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 124 120
Measure Type: Number
Unit of Measure: percentage of participants
74.2 71.1
8.Secondary Outcome
Title OS - High Baseline Plasma VEGF-A ITT Population
Hide Description OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.
Time Frame From randomization till death or clinical cut-off (up to 244 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
High Baseline Plasma VEGF-A ITT population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 124 120
Median (95% Confidence Interval)
Unit of Measure: months
19.4
(16.5 to 25.0)
22.8
(18.2 to 31.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Stratified analysis: Stratification factors were prior adjuvant chemotherapy (yes/no) and estrogen receptor / progesterone receptor status (positive, negative).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2745
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.63 to 1.14
Estimation Comments Hazards ratio was estimated by Cox regression.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Unstratified analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3616
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.65 to 1.17
Estimation Comments Hazards ratio was estimated by Cox regression.
9.Secondary Outcome
Title Percentage of Participants With an Objective Response - ITT Population
Hide Description Objective response was defined as having a Complete Response (CR) or Partial Response (PR) according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Measurable disease was defined by the presence of at least one measurable lesion by clinical measurement, chest x-ray, computed tomography (CT), or magnetic resonance imaging (MRI).
Time Frame Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed=participants from ITT population with measurable disease at baseline.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 214 202
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.2
(26.87 to 39.49)
54.0
(47.09 to 60.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 20.78
Confidence Interval (2-Sided) 95%
11.45 to 30.11
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With an Objective Response - High Baseline Plasma VEGF-A ITT Population
Hide Description Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Measurable disease was defined by the presence of at least one measurable lesion by clinical measurement, chest x-ray, CT, or MRI.
Time Frame Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed=participants from high baseline plasma VEGF-A ITT population with measurable disease at baseline.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 116 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
32.8
(24.22 to 41.30)
54.3
(44.76 to 63.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Fisher
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 21.53
Confidence Interval (2-Sided) 95%
8.73 to 34.32
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Duration of Response - ITT Population
Hide Description Duration of response was defined as the time from the initial date of the objective response to documented disease progression or death (whichever occurred first). Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. Analysis was performed using Kaplan Meier method.
Time Frame Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 117.7 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed=participants from ITT population who had an objective response.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 71 109
Median (95% Confidence Interval)
Unit of Measure: months
9.2
(7.4 to 11.5)
9.5
(7.8 to 12.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Stratified analysis: Stratification factors were plasma VEGF-A level (low/high), prior adjuvant chemotherapy (yes/no) and estrogen receptor / progesterone receptor status (positive, negative).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2737
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.54 to 1.19
Estimation Comments Hazards ratio was estimated by Cox regression.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Unstratified analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2959
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.56 to 1.19
Estimation Comments Hazards ratio was estimated by Cox regression.
12.Secondary Outcome
Title Duration of Response - High Baseline Plasma VEGF-A ITT Population
Hide Description Duration of response was defined as the time from the initial date of the objective response to documented disease progression or death (whichever occurred first). Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to <10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression was defined at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. Analysis was performed using Kaplan Meier method.
Time Frame Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 111.3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed=participants from high baseline plasma VEGF-A ITT population who had an objective response.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 38 57
Median (95% Confidence Interval)
Unit of Measure: months
7.2
(5.6 to 9.5)
8.1
(7.1 to 11.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Stratified analysis: Stratification factors were prior adjuvant chemotherapy (yes/no) and estrogen receptor / progesterone receptor status (positive, negative).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1783
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.41 to 1.18
Estimation Comments Hazards ratio was estimated by Cox regression.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paclitaxel+Placebo, Paclitaxel+ Bevacizumab
Comments Unstratified analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2429
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.45 to 1.22
Estimation Comments Hazards ratio was estimated by Cox regression.
13.Secondary Outcome
Title Percentage of Participants Who Were Alive at 1 Year - ITT Population
Hide Description [Not Specified]
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 242 239
Measure Type: Number
Unit of Measure: percentage of participants
80.94 82.47
14.Secondary Outcome
Title Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population
Hide Description [Not Specified]
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
High Baseline Plasma VEGF-A ITT Population
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description:
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
Overall Number of Participants Analyzed 124 120
Measure Type: Number
Unit of Measure: percentage of participants
69.27 80.96
Time Frame From the first dose of study drug through 30 days after the last dose of study drug or clinical cut-off (up to 115.1 weeks)
Adverse Event Reporting Description Safety population: All randomized participants who received at least one full or partial dose of any component of the study treatment (bevacizumab, placebo, or paclitaxel).
 
Arm/Group Title Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Hide Arm/Group Description Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and placebo matched to bevacizumab IV infusion on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death. Participants received paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 and bevacizumab IV 10 mg/kg on Days 1 and 15 of a 28 day cycle until progressive disease, treatment limiting toxicity or death.
All-Cause Mortality
Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   162/233 (69.53%)      161/238 (67.65%)    
Show Serious Adverse Events Hide Serious Adverse Events
Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/233 (19.31%)      66/238 (27.73%)    
Blood and lymphatic system disorders     
Anaemia * 1  2/233 (0.86%)  3 1/238 (0.42%)  3
Febrile neutropenia * 1  0/233 (0.00%)  0 4/238 (1.68%)  4
Leukopenia * 1  1/233 (0.43%)  1 1/238 (0.42%)  1
Neutropenia * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Cardiac disorders     
Atrial fibrillation * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Left ventricular dysfunction * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
ACUTE CORONARY SYNDROME * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
CARDIAC FAILURE CONGESTIVE * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Eye disorders     
Optic nerve disorder * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Visual acuity reduced * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
CATARACT * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Abdominal pain * 1  4/233 (1.72%)  6 2/238 (0.84%)  3
Colitis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Constipation * 1  1/233 (0.43%)  1 1/238 (0.42%)  2
Diarrhoea * 1  0/233 (0.00%)  0 2/238 (0.84%)  2
Duodenal obstruction * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Dyspepsia * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Enteritis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Gastric ulcer * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Gastric ulcer haemorrhage * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Gastric varices haemorrhage * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Haematochezia * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Nausea * 1  0/233 (0.00%)  0 4/238 (1.68%)  4
Pancreatitis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Small intestinal obstruction * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Vomiting * 1  3/233 (1.29%)  3 4/238 (1.68%)  4
General disorders     
Asthenia * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Death * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Influenza like illness * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Malaise * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Mucosal inflammation * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Pyrexia * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Sudden death * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
CATHETER SITE ERYTHEMA * 1  0/233 (0.00%)  0 1/238 (0.42%)  2
Hepatobiliary disorders     
Bile duct obstruction * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Cholecystitis * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Cholecystitis acute * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Gallbladder pain * 1  1/233 (0.43%)  3 0/238 (0.00%)  0
Hepatic failure * 1  0/233 (0.00%)  0 3/238 (1.26%)  3
Hyperbilirubinaemia * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Immune system disorders     
Drug hypersensitivity * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
ANAPHYLACTIC REACTION * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Infections and infestations     
Abdominal wall abscess * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Abscess * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Abscess limb * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Appendicitis * 1  0/233 (0.00%)  0 2/238 (0.84%)  2
Cellulitis * 1  0/233 (0.00%)  0 4/238 (1.68%)  6
Cholecystitis infective * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Colonic abscess * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Cystitis * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Device related infection * 1  2/233 (0.86%)  2 3/238 (1.26%)  3
Device related sepsis * 1  0/233 (0.00%)  1/238 (0.42%) 
Gastroenteritis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Infection * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Influenza * 1  0/233 (0.00%)  0 2/238 (0.84%)  2
Lung infection * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Peritonitis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Pharyngotonsillitis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Pneumonia * 1  3/233 (1.29%)  4 4/238 (1.68%)  4
Pneumonia necrotising * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Sepsis * 1  1/233 (0.43%)  1 2/238 (0.84%)  2
Sepsis syndrome * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Septic shock * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Upper respiratory tract infection * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Urinary tract infection * 1  1/233 (0.43%)  1 2/238 (0.84%)  2
Wound infection bacterial * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
VIRAL INFECTION * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
CATHETER SITE INFECTION * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
KLEBSIELLA SEPSIS * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
SOFT TISSUE INFECTION * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
URINARY TRACT INFECTION BACTERIAL * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Injury, poisoning and procedural complications     
Femoral neck fracture * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Femur fracture * 1  0/233 (0.00%)  0 2/238 (0.84%)  2
Hip fracture * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Humerus fracture * 1  0/233 (0.00%)  0 2/238 (0.84%)  2
ROAD TRAFFIC ACCIDENT * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
STERNAL FRACTURE * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
WOUND DEHISCENCE * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Investigations     
Urine output decreased * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Metabolism and nutrition disorders     
Decreased appetite * 1  2/233 (0.86%)  2 0/238 (0.00%)  0
Type 2 diabetes mellitus * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
HYPOKALAEMIA * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
HYPONATRAEMIA * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
LACTIC ACIDOSIS * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Musculoskeletal and connective tissue disorders     
Back pain * 1  0/233 (0.00%)  0 4/238 (1.68%)  4
Neck pain * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Osteonecrosis of jaw * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Gastric cancer * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Nervous system disorders     
Cerebral ischaemia * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Dementia * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Dizziness * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Hemiparesis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Loss of consciousness * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Speech disorder * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Spinal cord compression * 1  1/233 (0.43%)  0/238 (0.00%)  0
Syncope * 1  1/233 (0.43%)  1 3/238 (1.26%)  4
Renal and urinary disorders     
Cystitis haemorrhagic * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Haematuria * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Bronchospasm * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Dyspnoea * 1  2/233 (0.86%)  2 0/238 (0.00%)  0
Pleural effusion * 1  2/233 (0.86%)  2 0/238 (0.00%)  0
Pneumonitis * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Pneumothorax * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Pulmonary embolism * 1  0/233 (0.00%)  0 4/238 (1.68%)  4
Pulmonary oedema * 1  2/233 (0.86%)  2 0/238 (0.00%)  0
Skin and subcutaneous tissue disorders     
Pain of skin * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Skin haemorrhage * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Vascular disorders     
Aortic stenosis * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Deep vein thrombosis * 1  2/233 (0.86%)  2 0/238 (0.00%)  0
Embolism venous * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
Superior vena cava syndrome * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
Venous thrombosis limb * 1  1/233 (0.43%)  1 0/238 (0.00%)  0
ARTERIAL THROMBOSIS * 1  0/233 (0.00%)  0 1/238 (0.42%)  1
1
Term from vocabulary, MedDRA (17.1)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Paclitaxel+Placebo Paclitaxel+ Bevacizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   225/233 (96.57%)      230/238 (96.64%)    
Blood and lymphatic system disorders     
Anaemia * 1  39/233 (16.74%)  82 39/238 (16.39%)  63
Leukopenia * 1  14/233 (6.01%)  42 17/238 (7.14%)  41
Neutropenia * 1  50/233 (21.46%)  124 77/238 (32.35%)  254
Gastrointestinal disorders     
Abdominal pain * 1  17/233 (7.30%)  30 20/238 (8.40%)  27
Abdominal pain upper * 1  13/233 (5.58%)  14 13/238 (5.46%)  16
Constipation * 1  50/233 (21.46%)  70 67/238 (28.15%)  108
Diarrhoea * 1  72/233 (30.90%)  128 88/238 (36.97%)  189
Dyspepsia * 1  16/233 (6.87%)  20 23/238 (9.66%)  40
Nausea * 1  75/233 (32.19%)  205 99/238 (41.60%)  310
Stomatitis * 1  26/233 (11.16%)  35 42/238 (17.65%)  75
Toothache * 1  8/233 (3.43%)  9 15/238 (6.30%)  16
Vomiting * 1  36/233 (15.45%)  63 47/238 (19.75%)  96
General disorders     
Asthenia * 1  36/233 (15.45%)  50 32/238 (13.45%)  62
Fatigue * 1  74/233 (31.76%)  123 88/238 (36.97%)  156
Oedema peripheral * 1  42/233 (18.03%)  57 41/238 (17.23%)  56
Pyrexia * 1  28/233 (12.02%)  37 34/238 (14.29%)  59
Infections and infestations     
Bronchitis * 1  12/233 (5.15%)  12 11/238 (4.62%)  14
Nasopharyngitis * 1  36/233 (15.45%)  65 24/238 (10.08%)  54
Paronychia * 1  7/233 (3.00%)  9 13/238 (5.46%)  13
Upper respiratory tract infection * 1  11/233 (4.72%)  14 25/238 (10.50%)  26
Urinary tract infection * 1  16/233 (6.87%)  22 35/238 (14.71%)  47
SINUSITIS * 1  8/233 (3.43%)  12 12/238 (5.04%)  15
Investigations     
Alanine aminotransferase increased * 1  17/233 (7.30%)  21 21/238 (8.82%)  37
Aspartate aminotransferase increased * 1  16/233 (6.87%)  19 21/238 (8.82%)  32
Neutrophil count decreased * 1  20/233 (8.58%)  100 15/238 (6.30%)  56
White blood cell count decreased * 1  16/233 (6.87%)  84 21/238 (8.82%)  87
WEIGHT DECREASED * 1  5/233 (2.15%)  5 12/238 (5.04%)  13
Metabolism and nutrition disorders     
Decreased appetite * 1  42/233 (18.03%)  65 55/238 (23.11%)  91
Hypokalaemia * 1  10/233 (4.29%)  13 15/238 (6.30%)  22
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  53/233 (22.75%)  86 53/238 (22.27%)  91
Back pain * 1  31/233 (13.30%)  42 26/238 (10.92%)  32
Bone pain * 1  20/233 (8.58%)  32 11/238 (4.62%)  17
Myalgia * 1  28/233 (12.02%)  60 43/238 (18.07%)  83
Pain in extremity * 1  21/233 (9.01%)  23 23/238 (9.66%)  32
NECK PAIN * 1  3/233 (1.29%)  5 12/238 (5.04%)  13
MUSCULOSKELETAL PAIN * 1  5/233 (2.15%)  8 12/238 (5.04%)  14
Nervous system disorders     
Dizziness * 1  24/233 (10.30%)  25 28/238 (11.76%)  33
Dysgeusia * 1  22/233 (9.44%)  24 33/238 (13.87%)  43
Headache * 1  44/233 (18.88%)  71 51/238 (21.43%)  85
Neuropathy peripheral * 1  50/233 (21.46%)  67 47/238 (19.75%)  72
Paraesthesia * 1  17/233 (7.30%)  21 12/238 (5.04%)  14
Peripheral sensory neuropathy * 1  84/233 (36.05%)  107 92/238 (38.66%)  129
Psychiatric disorders     
Anxiety * 1  15/233 (6.44%)  15 8/238 (3.36%)  8
Insomnia * 1  20/233 (8.58%)  24 35/238 (14.71%)  46
Renal and urinary disorders     
Proteinuria * 1  26/233 (11.16%)  33 32/238 (13.45%)  53
Respiratory, thoracic and mediastinal disorders     
Cough * 1  30/233 (12.88%)  38 43/238 (18.07%)  59
Dysphonia * 1  5/233 (2.15%)  5 19/238 (7.98%)  24
Dyspnoea * 1  30/233 (12.88%)  33 33/238 (13.87%)  41
Epistaxis * 1  48/233 (20.60%)  77 97/238 (40.76%)  158
Oropharyngeal pain * 1  14/233 (6.01%)  15 18/238 (7.56%)  23
Rhinorrhoea * 1  3/233 (1.29%)  4 20/238 (8.40%)  26
Skin and subcutaneous tissue disorders     
Alopecia * 1  145/233 (62.23%)  159 140/238 (58.82%)  149
Dry skin * 1  7/233 (3.00%)  7 18/238 (7.56%)  20
Nail discolouration * 1  18/233 (7.73%)  18 33/238 (13.87%)  37
Nail disorder * 1  13/233 (5.58%)  13 13/238 (5.46%)  14
Onychomadesis * 1  6/233 (2.58%)  6 15/238 (6.30%)  17
Pruritis * 1  10/233 (4.29%)  12 15/238 (6.30%)  17
Rash * 1  31/233 (13.30%)  36 58/238 (24.37%)  113
Vascular disorders     
Hot flush * 1  10/233 (4.29%)  30 15/238 (6.30%)  17
Hypertension * 1  30/233 (12.88%)  83 73/238 (30.67%)  109
1
Term from vocabulary, MedDRA (17.1)
*
Indicates events were collected by non-systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01663727     History of Changes
Other Study ID Numbers: GO25632
2011-005335-97 ( EudraCT Number )
First Submitted: August 9, 2012
First Posted: August 13, 2012
Results First Submitted: January 12, 2016
Results First Posted: February 10, 2016
Last Update Posted: January 21, 2019