Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) in Patients With Inflammatory or Locally Advanced Breast Cancer (NCT NCT00559845)

NCT ID: NCT00559845

Last Updated: 2018-04-09

Results Overview

Pathological complete response was defined as absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 56 participants
• Primary outcome timeframe: Up to 7.5 years
• Results posted on: 2018-04-09

Participant Flow

56 participants were enrolled in 8 centers in Italy.

Participant milestones

Measure	Bevacizumab 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC), followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 milligrams per meter squared (mg/m\^2) intravenous (i.v.) bolus over ≤15 minutes (min); epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 milligrams per kilogram (mg/kg) i.v. every 2 weeks for 6 cycles.
Overall Study STARTED	56
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Bevacizumab 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC), followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 milligrams per meter squared (mg/m\^2) intravenous (i.v.) bolus over ≤15 minutes (min); epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 milligrams per kilogram (mg/kg) i.v. every 2 weeks for 6 cycles.
Overall Study Withdrew Consent	1
Overall Study Disease Progression	1
Overall Study Adverse Event	3
Overall Study Did Not Attend Cycle 6 Hospital Visit	1
Overall Study Premature Surgery-Investigator Decision	1

Baseline Characteristics

A Study of Avastin (Bevacizumab) in Patients With Inflammatory or Locally Advanced Breast Cancer

Baseline characteristics by cohort

Measure	Bevacizumab n=56 Participants FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.
Age, Continuous	50.00 years STANDARD_DEVIATION 9.279 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 7.5 years

Population: Intention-to-Treat (ITT) population, defined as all participants that were included in the trial and underwent surgery.

Pathological complete response was defined as absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy.

Outcome measures

Measure

Bevacizumab n=56 Participants FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.

Percentage of Participants With Pathological Complete Response Following Principle Investigator Review

23.2 percentage of participants

SECONDARY outcome

Timeframe: Up to 7.5 years

Population: ITT population, defined as all participants that were included in the trial and underwent surgery.

Objective response rate was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions; PR was defined as a 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Measure

Bevacizumab n=56 Participants FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.

Objective Response Rate

59.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 7.5 years

Population: ITT population, defined as all participants that were included in the trial and underwent surgery.

Rate of breast conversing surgery is defined as percentage of participants who achieved breast conversing surgery out of the ITT population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant treatment.

Outcome measures

Measure	Bevacizumab n=56 Participants FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.
Percentage of Participants With Breast-Conserving Surgery Breast-conserving	17.0 percentage of participants
Percentage of Participants With Breast-Conserving Surgery Breast-conserving Plus Axillary Dissection	13.2 percentage of participants

SECONDARY outcome

Timeframe: Months 12, 24, 36, 48, and 60

Population: ITT population, defined as all participants that were included in the trial and underwent surgery. Here, number of participants analyzed signifies those participants who were evaluable for the outcome measure.

Disease-free interval was defined as the time from enrollment until recurrence of tumor or death from any cause, and was estimated using the Kaplan-Meier method. The percentage of participants without events at Months 12, 24, 36, 48, and 60 is presented.

Outcome measures

Measure	Bevacizumab n=53 Participants FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.
Percentage of Participants With Disease-Free Interval 12 Months	92.2 percentage of participants Interval 85.1 to 99.8
Percentage of Participants With Disease-Free Interval 24 Months	84.3 percentage of participants Interval 74.9 to 94.9
Percentage of Participants With Disease-Free Interval 36 Months	80.4 percentage of participants Interval 70.2 to 92.1
Percentage of Participants With Disease-Free Interval 48 Months	76.5 percentage of participants Interval 65.7 to 89.1
Percentage of Participants With Disease-Free Interval 60 Months	76.5 percentage of participants Interval 65.7 to 89.1

SECONDARY outcome

Timeframe: Up to 7.5 years

Population: Data for the outcome measure was not collected.

Overall survival was defined as the time from enrollment of participant to death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7.5 years

Population: Safety population, defined as all participants who received at least one infusion of Bevacizumab.

An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Outcome measures

Measure

Bevacizumab n=56 Participants FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.

Percentage of Participants Experiencing Any Adverse Event

100.0 percentage of participants

Adverse Events

Bevacizumab

Serious events: 8 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab n=54 participants at risk FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.
Blood and lymphatic system disorders Anaemia	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Blood and lymphatic system disorders Febrile Neutropenia	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Eye disorders Retinopathy Hypertensive	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Infections and infestations Febrile Infection	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Injury, poisoning and procedural complications Postoperative Wound Complication	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Investigations Cardiac Imaging Procedure Abnormal	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Melanoma In Situ	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Psychiatric disorders Suicide Attempt	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 1/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.

Other adverse events

Measure	Bevacizumab n=54 participants at risk FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months. FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles. Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks. Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles.
Blood and lymphatic system disorders Neutropenia	40.7% 22/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Blood and lymphatic system disorders Leukopenia	27.8% 15/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Blood and lymphatic system disorders Anaemia	22.2% 12/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Eye disorders Conjunctivitis	16.7% 9/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Nausea	70.4% 38/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Diarrhea	31.5% 17/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Vomiting	31.5% 17/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Constipation	20.4% 11/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Stomatitis	20.4% 11/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Abdominal Pain Upper	13.0% 7/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Dyspepsia	11.1% 6/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Haemorrhoids	7.4% 4/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Gastrointestinal disorders Abdominal Pain	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
General disorders Asthenia	55.6% 30/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
General disorders Mucosal Inflammation	33.3% 18/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
General disorders Pyrexia	27.8% 15/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
General disorders Oedema	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
General disorders Pain	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Investigations Alanine Aminotransferase Increased	11.1% 6/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Investigations Ast Increased	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 18/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Musculoskeletal and connective tissue disorders Bone Pain	24.1% 13/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Musculoskeletal and connective tissue disorders Pain In Extremity	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Nervous system disorders Paraesthesia	50.0% 27/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Nervous system disorders Headache	18.5% 10/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Nervous system disorders Dysgeusia	9.3% 5/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Nervous system disorders Syncope	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Psychiatric disorders Anxiety	7.4% 4/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Respiratory, thoracic and mediastinal disorders Epistaxis	61.1% 33/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 4/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Skin and subcutaneous tissue disorders Alopecia	66.7% 36/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Skin and subcutaneous tissue disorders Nail Disorder	18.5% 10/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Skin and subcutaneous tissue disorders Rash	14.8% 8/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Skin and subcutaneous tissue disorders Pruritus	7.4% 4/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Skin and subcutaneous tissue disorders Erythema	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Surgical and medical procedures Astringent Therapy	5.6% 3/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Vascular disorders Hypertension	24.1% 13/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.
Vascular disorders Phlebitis	7.4% 4/54 • Up to 7.5 years Safety population defined as all participants who received at least one infusion of Bevacizumab.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.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