Trial Outcomes & Findings for AVAREG Study: An Observational Study of Avastin (Bevacizumab) in Patients With Metastatic Breast Cancer (NCT NCT01777932)

NCT ID: NCT01777932

Last Updated: 2016-02-05

Results Overview

Progression free survival (PFS) was assessed based on time to tumour progression or death (whichever occurred first) from the start of bevacizumab treatment.

• Recruitment status: COMPLETED
• Target enrollment: 220 participants
• Primary outcome timeframe: Approximately 5 years
• Results posted on: 2016-02-05

Participant Flow

A total of 220 participants were enrolled across 34 centers in Hungary from 20 December 2007 to 08 March 2011.

Participant milestones

Measure	Paclitaxel + Bevacizumab Arm Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Overall Study STARTED	220
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	205

Reasons for withdrawal

Measure	Paclitaxel + Bevacizumab Arm Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Overall Study Disease progression	136
Overall Study Death	3
Overall Study Adverse Event	34
Overall Study Lost to Follow-up	3
Overall Study Investigator decision	10
Overall Study Reimbursement limit	9
Overall Study Patient refused further treatment	10

Baseline Characteristics

AVAREG Study: An Observational Study of Avastin (Bevacizumab) in Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	187 Participants n=5 Participants
Age, Categorical >=65 years	33 Participants n=5 Participants
Sex/Gender, Customized Female	218 participants n=5 Participants
Sex/Gender, Customized Male	1 participants n=5 Participants
Sex/Gender, Customized Missing/unknown	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 5 years

Population: All enrolled participants were considered for this outcome measure.

Progression free survival (PFS) was assessed based on time to tumour progression or death (whichever occurred first) from the start of bevacizumab treatment.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Progression Free Survival	9.3 months Interval 7.8 to 10.8

SECONDARY outcome

Timeframe: Approximately 5 years

Population: All enrolled participants were considered for this outcome measure.

The status of participants whether alive, dead, unknown or missing one year after the start of bevacizumab treatment is reported.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
One Year Survival Alive	150 participants
One Year Survival Died	37 participants
One Year Survival Unknown	13 participants
One Year Survival Missing	20 participants

SECONDARY outcome

Timeframe: Approximately 5 years

Population: All enrolled participants were considered for this outcome measure.

Time to treatment discontinuation is defined as the time to change of therapy due to any cause (tumour progression, toxicity, or other causes) from the start of bevacizumab treatment.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Time to Discontinuation (TTD) of Bevacizumab Treatment	7.0 months Interval 6.05 to 7.95

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: All enrolled participants were considered for this outcome measure.

The hormone receptor status for Oestrogen (ER), Progesterone (PgR) and Human epidermal growth factor receptor (HER-2) is reported as positive, negative, unknown or missing.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Participants With Hormone Receptor Status at Diagnosis ER positive	98 participants
Participants With Hormone Receptor Status at Diagnosis ER negative	117 participants
Participants With Hormone Receptor Status at Diagnosis ER unknown	3 participants
Participants With Hormone Receptor Status at Diagnosis ER missing	2 participants
Participants With Hormone Receptor Status at Diagnosis PgR positive	90 participants
Participants With Hormone Receptor Status at Diagnosis PgR negative	125 participants
Participants With Hormone Receptor Status at Diagnosis PgR unknown	3 participants
Participants With Hormone Receptor Status at Diagnosis PgR missing	2 participants
Participants With Hormone Receptor Status at Diagnosis HER-2 positive	5 participants
Participants With Hormone Receptor Status at Diagnosis HER-2 negative	212 participants
Participants With Hormone Receptor Status at Diagnosis HER-2 unknown	2 participants
Participants With Hormone Receptor Status at Diagnosis HER-2 missing	1 participants

SECONDARY outcome

Timeframe: Approximately 5 years

Population: All enrolled participants were considered for this outcome measure. Out of the total 220 enrolled participants, 106 participants were triple negative, 110 were not triple negative and data for 4 participants were missing.

PFS was assessed based on time to tumour progression or death (whichever occurred first) from the start of bevacizumab treatment for participants with triple negative status and not triple negative status.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Progression Free Survival in Participants With Triple Negative Receptor Status at Study Entry Triple negative (n=106)	8.30 months Interval 7.76 to 8.84
Progression Free Survival in Participants With Triple Negative Receptor Status at Study Entry Not triple negative (n=110)	13.30 months Interval 10.98 to 15.63

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: All enrolled participants were considered for this outcome measure.

Number of participants at each Metastatic breast cancer stage 0, I, II, III or IV, at the point of diagnosis is reported.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Participants With Tumor Stage at Diagnosis Tumor stage 0	1 participants
Participants With Tumor Stage at Diagnosis Tumor stage I	38 participants
Participants With Tumor Stage at Diagnosis Tumor stage II	87 participants
Participants With Tumor Stage at Diagnosis Tumor stage III	39 participants
Participants With Tumor Stage at Diagnosis Tumor stage IV	50 participants
Participants With Tumor Stage at Diagnosis Missing	5 participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: All enrolled participants were considered for this outcome measure.

The Eastern Cooperative Oncology Group (ECOG) status for participants was categorized as 0, 1, 2, or missing. ECOG has 4 grades as: 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care, totally confined to bed/chair.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Participants With Eastern Cooperative Oncology Group Status at Study Entry ECOG stage 0	164 participants
Participants With Eastern Cooperative Oncology Group Status at Study Entry ECOG stage 1	45 participants
Participants With Eastern Cooperative Oncology Group Status at Study Entry ECOG stage 2	7 participants
Participants With Eastern Cooperative Oncology Group Status at Study Entry Missing	4 participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: All enrolled participants were considered for this outcome measure

The status of prior therapy (i.e. chemotherapy, endocrine therapy, and radiotherapy) at study entry (baseline) is reported.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Participants With Prior Therapy at Study Entry (Baseline) Prior endocrine treatment, Yes	64 participants
Participants With Prior Therapy at Study Entry (Baseline) Prior endocrine treatment, No	152 participants
Participants With Prior Therapy at Study Entry (Baseline) Prior endocrine treatment, Unknown	1 participants
Participants With Prior Therapy at Study Entry (Baseline) Prior endocrine treatment, Missing	3 participants
Participants With Prior Therapy at Study Entry (Baseline) Prior radiotherapy, Yes	135 participants
Participants With Prior Therapy at Study Entry (Baseline) Prior radiotherapy, No	80 participants
Participants With Prior Therapy at Study Entry (Baseline) Prior radiotherapy, Unknown	2 participants
Participants With Prior Therapy at Study Entry (Baseline) Prior radiotherapy, Missing	3 participants
Participants With Prior Therapy at Study Entry (Baseline) Previous chemotherapy, Yes	127 participants
Participants With Prior Therapy at Study Entry (Baseline) Previous chemotherapy, No	83 participants
Participants With Prior Therapy at Study Entry (Baseline) Previous chemotherapy, Unknown	2 participants
Participants With Prior Therapy at Study Entry (Baseline) Previous chemotherapy, Missing	8 participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: All enrolled participants were considered for this outcome measure.

Participant's history at the time of diagnosis of metastatic disease and sites of metastases is reported at study entry (baseline).

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Participants With Disease History at Study Entry (Baseline) Missing	6 participants
Participants With Disease History at Study Entry (Baseline) At time of initial diagnosis	44 participants
Participants With Disease History at Study Entry (Baseline) < = 2 years after diagnosis	91 participants
Participants With Disease History at Study Entry (Baseline) > 2 years after diagnosis	79 participants
Participants With Disease History at Study Entry (Baseline) Metastatic site, bone	101 participants
Participants With Disease History at Study Entry (Baseline) Metastatic site, lung	96 participants
Participants With Disease History at Study Entry (Baseline) Metastatic site, liver	65 participants
Participants With Disease History at Study Entry (Baseline) Metastatic site, other	127 participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: All enrolled participants were considered for this outcome measure.

The type of metastases (bone and visceral) are reported at study entry (baseline) is reported.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Participants With Type of Metastases at Study Entry (Baseline) Only Bone metastases, Yes	16 participants
Participants With Type of Metastases at Study Entry (Baseline) Only Bone metastases, No	196 participants
Participants With Type of Metastases at Study Entry (Baseline) Only Bone metastases, Missing	8 participants
Participants With Type of Metastases at Study Entry (Baseline) Only Visceral metastases, Yes	113 participants
Participants With Type of Metastases at Study Entry (Baseline) Only Visceral metastases, No	100 participants
Participants With Type of Metastases at Study Entry (Baseline) Only Visceral metastases, Missing	7 participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: All enrolled participants were considered for this outcome measure

The number of participants with proteinurea status as positive, negative or missing is reported.

Outcome measures

Measure	Paclitaxel + Bevacizumab Arm n=220 Participants Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Participants With Proteinuria at Study Entry (Baseline) Positive	3 participants
Participants With Proteinuria at Study Entry (Baseline) Negative	215 participants
Participants With Proteinuria at Study Entry (Baseline) Missing	2 participants

Adverse Events

Paclitaxel + Bevacizumab Arm

Serious events: 19 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Measure	Paclitaxel + Bevacizumab Arm n=220 participants at risk Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Blood and lymphatic system disorders Anaemia	1.4% 3/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Blood and lymphatic system disorders Febrile neutropenia	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Blood and lymphatic system disorders Thrombocytopenia	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Cardiac disorders Acute myocardial infarction	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Cardiac disorders Cardiomyopathy	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Cardiac disorders Myocardial infarction	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Gastrointestinal disorders Gastric perforation	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
General disorders Pain	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Hepatobiliary disorders Acute hepatic failure	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Hepatobiliary disorders Jaundice	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Infections and infestations Peritonitis	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Infections and infestations Sepsis	0.91% 2/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Investigations Blood creatinine increased	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Investigations Blood urea increased	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Metabolism and nutrition disorders Hyperglycaemia	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Renal and urinary disorders Nephropathy toxic	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Infections and infestations Pneumonia	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Renal and urinary disorders Proteinuria	1.4% 3/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.91% 2/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Vascular disorders Embolism venous	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Vascular disorders Thrombophlebitis	0.45% 1/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.

Other adverse events

Measure	Paclitaxel + Bevacizumab Arm n=220 participants at risk Participants received licensed dose regimens of bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until disease progression, or unacceptable toxicity (whichever occurred first), in accordance with the summary of product characteristics. Paclitaxel could be administered weekly or every 3 weeks according to the accepted oncology protocol.
Blood and lymphatic system disorders Anaemia	1.8% 4/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Blood and lymphatic system disorders Leucopenia	2.3% 5/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Blood and lymphatic system disorders Neutropenia	1.8% 4/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
General disorders Asthenia	4.1% 9/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Infections and infestations Upper respiratory tract infection	1.4% 3/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Nervous system disorders Neuropathy peripheral	3.2% 7/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Nervous system disorders Paraesthesia	2.3% 5/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Nervous system disorders Polyneuropathy	2.3% 5/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Renal and urinary disorders Proteinuria	2.3% 5/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.2% 7/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	1.4% 3/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Skin and subcutaneous tissue disorders Alopecia	1.8% 4/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Skin and subcutaneous tissue disorders Nail disorder	1.8% 4/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.
Vascular disorders Hypertension	2.7% 6/220 • Approximately 5 years Serious adverse events and non-serious adverse events are reported in all enrolled participants.

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: global.trial_information@roche.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER