An Observational Study of Avastin (Bevacizumab) in Patients With HER2-metastatic or Locally Advanced Breast Cancer

Completed

• Conditions: Breast Cancer

• Registration Number: NCT01461044
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This observational study will evaluate the safety and efficacy of triple negative or HR+ patients with HER2-metastatic or locally advanced breast cancer treated with Avastin (bevacizumab) as first line therapy for at least 12 months and without disease progression for at least 12 months. Data will be collected retrospectively (from the diagnosis to the inclusion in the study) and for 18 months from study start.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2011-10-24
• Study First Submitted QC: 2011-10-26
• Study First Posted: 2011-10-27
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Results First Submitted: 2015-10-22
• Status Verified: 2015-12
• Results First Submitted QC: 2015-12-18
• Last Update Submitted: 2015-12-18
• Results First Posted: 2016-01-26
• Last Update Posted: 2016-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

• Adult patients, >/=18 years of age
• HER2-metastatic breast cancer or locally advanced breast cancer
• Patients with Avastin as first line therapy administered for at least 12 months
• Patients without disease progression after the beginning of Avastin treatment for at least 12 months

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Exclusion Criteria

• Patients not willing to give informed consent

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Disease-Free Interval	From initial diagnosis to the diagnosis of metastatic disease (up to a maximum of 260 months, assessed retrospectively at Baseline)	Disease free interval was expressed in months: (Date of diagnosis of metastatic disease - Date of initial diagnosis + 1) / 30.4375. Disease free interval was observed retrospectively and assessed at inclusion period or baseline (the time after the retrospective phase and at the start of prospective phase).
Mean Body Weight at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants Classified Based on Number of Metastatic Sites at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Percentage of participants that reported metastatic disease in less than or equal to (\<=) 3 sites or greater than (\>) 3 sites were assessed. Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Progesterone Receptors (PR) at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Ki67 (MiB1) at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	The Ki67 (MiB1) a prognostic marker, is used to evaluate the proliferative activity of breast cancer. Percentage of participants with \< or \>=10% and unknown were reported. Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants Who Were Disease-Free for at Least 24 Months After Initial Diagnosis	From initial diagnosis to the diagnosis of metastatic disease (up to a maximum of 260 months, assessed retrospectively at Baseline)	Disease free interval was expressed in months: (Date of diagnosis of metastatic disease - Date of initial diagnosis + 1) / 30.4375. Percentage of participants who were disease-free for at least 24 months were reported.
Mean Body Mass Index (BMI) at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Breast Cancer (BRCA) Mutation at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Negative HER2 Status at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants Who Received First-Line Endocrine Therapy at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Menopausal Status at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Menopausal status included premenopausal and menopausal. Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Visceral Involvement at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Previous and Concurrent Disease at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants Who Were Disease-Free for at Least 12 Months After Initial Diagnosis	From initial diagnosis to the diagnosis of metastatic disease (up to a maximum of 260 months, assessed retrospectively at Baseline)	Disease free interval was expressed in months: (Date of diagnosis of metastatic disease - Date of initial diagnosis + 1) / 30.4375. Percentage of participants who were disease-free for at least 12 months were reported.
Percentage of Participants With Cross Results for Both ER and PR at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	ECOG-PS measured on-therapy (time between first dose and last dose date with a 30-day lag) assessed participant's performance status on a 5 point scale: 0 equals (=) fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, but ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than \[\>\] 50 percentage \[%\] of waking hours \[h\]), capable of all self care, but unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any selfcare, totally confined to bed or chair and 5=Dead. Only participants that reported in any of the specified scale was reported. Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Metastatic Disease at Identified Metastatic Sites at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Metastatic diseases were identified at bone, lung, liver, central nervous system, soft tissue, lymph nodes, skin, pleura and other sites. Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Estrogen Receptors (ER) at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Mean Age at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Mean Height at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With HR Status at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).
Percentage of Participants With Mitotic Index (MI) at the Time of Local or Metastatic Progression	At the time of Advanced or Metastatic Diagnosis (up to a maximum of 260 months, assessed retrospectively at Baseline)	MI is an indirect measure of cell proliferation that has been demonstrated to be a strong predictor of outcome for several human and canine cancers. Percentage of participants that reported a low, intermediate, high and unknown indices were included. Time of local or metastatic progression is the time of advanced or metastatic diagnosis which was assessed at inclusion or baseline (the time after the retrospective phase and at the start of prospective phase).

Secondary Outcome Measures

Name	Time	Method
Time to Progression	From first administration of bevacizumab to inclusion in the study (up to a maximum of 42.8 months, assessed retrospectively at Baseline)	Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Participants who withdrew from the study early for insufficient therapeutic response without tumor assessment for PD were also included within the definition of PD. Time to progression was defined as the time from treatment start to PD. Participants who did not experience PD were censored from the last tumor assessment. Time to progression was estimated using Kaplan-Meier and expressed in months. Inclusion (baseline) here was the time after the retrospective phase and at the start of prospective phase.
Percentage of Participants With Death	From the first administration of bevacizumab to death from any cause (up to a maximum of 60.8 months including retrospective and prospective treatment)	Overall survival (OS) was defined as the time between the first administration of bevacizumab and death from any cause and participants still alive at the end of the study were censored at the last consultation or last contact date.
Percentage of Participants With Disease Progression or Death	From first administration of bevacizumab to inclusion in the study (up to a maximum of 42.8 months , assessed retrospectively at Baseline)	Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death"). PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment.
Progression-Free Survival	From first administration of bevacizumab to inclusion in the study (up to a maximum of 42.8 months, assessed retrospectively at Baseline)	Progression-free survival was defined as the time from first dose of bevacizumab to documented PD or death from any cause, whichever occurred first. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Inclusion (baseline) here was the time after the retrospective phase and at the start of prospective phase.
Percentage of Participants Who Maintained Bevacizumab Beyond the First Progressive Disease	From start of bevacizumab until 18 months after inclusion (up to a maximum of 60.8 months including retrospective and prospective treatment)
Overall Survival (OS)	From the first administration of bevacizumab to death from any cause (up to a maximum of 60.8 months including retrospective and prospective treatment)	OS was defined as the time between the first administration of bevacizumab and death from any cause and participants still alive at the end of the study were censored at the last consultation or last contact date.
Duration of Bevacizumab as First Line Treatment	From start of bevacizumab until 18 months after inclusion (up to a maximum of 60.8 months including retrospective and prospective treatment)
Percentage of Participants Who Received Induction Therapy in Combination With Bevacizumab	From start of bevacizumab until 18 months after inclusion (up to a maximum of 60.8 months including retrospective and prospective treatment)
Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR)	From first administration of bevacizumab to inclusion in the study (up to a maximum of 42.8 months , assessed retrospectively at Baseline)	Objective tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR was defined as the disappearance of all target and non-target lesions, and confirmed PR was defined as at least at 30% decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Inclusion (baseline) here was the time after the retrospective phase and at the start of prospective phase.
Percentage of Participants With Temporary Discontinuation	From start of bevacizumab until 18 months after inclusion (up to a maximum of 60.8 months including retrospective and prospective treatment)
Percentage of Participants With Reasons for Definitive Discontinuation	From start of bevacizumab until 18 months after inclusion (up to a maximum of 60.8 months including retrospective and prospective treatment)
Percentage of Participants With Reasons for Temporary Discontinuation	From start of bevacizumab until 18 months after inclusion (up to a maximum of 60.8 months including retrospective and prospective treatment)
Percentage of Participants With Definitive Discontinuation	From start of bevacizumab until 18 months after inclusion (up to a maximum of 60.8 months including retrospective and prospective treatment)