Trial Outcomes & Findings for BEATRICE Study: A Study of Bevacizumab (Avastin) Adjuvant Therapy in Triple Negative Breast Cancer (NCT NCT00528567)

Last Updated: 2015-09-04

Results Overview

IDFS, was a composite endpoint defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site);Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer or Second primary non-breast invasive cancer.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2591 participants

Primary outcome timeframe

Event driven (until data cutoff: 29 February 2012: up to 49 months)

Results posted on

2015-09-04

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab and Chemotherapy Participants randomized to receive bevacizumab and chemotherapy. For these patients, bevacizumab was given in combination with chemotherapy at a dose of 5 mg/kg/week equivalent using 1 of 3 different scheduling options depending on the schedule of the adjuvant chemotherapy selected. After completing chemotherapy + bevacizumab (treatment period 1), patients in this arm received bevacizumab monotherapy up to a total duration of 1 year (treatment period 2). At the end of treatment (i.e., after approximately 55 weeks), patients were followed up until the end of the study.	Chemotherapy Participants randomized to receive chemotherapy alone. For patients randomized to the chemotherapy alone arm, investigators could select from one of three chemotherapy regimens. After completing chemotherapy (treatment period 1) patients entered a post-treatment surveillance period for the remainder of the first year after randomization (treatment period 2). At the end of treatment (i.e., after approximately 55 weeks), patients were followed up until the end of the study.
Overall Study STARTED	1301	1290
Overall Study Intention to Treat	1301	1290
Overall Study Safety Population	1288	1271
Overall Study COMPLETED	870	982
Overall Study NOT COMPLETED	431	308

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab and Chemotherapy Participants randomized to receive bevacizumab and chemotherapy. For these patients, bevacizumab was given in combination with chemotherapy at a dose of 5 mg/kg/week equivalent using 1 of 3 different scheduling options depending on the schedule of the adjuvant chemotherapy selected. After completing chemotherapy + bevacizumab (treatment period 1), patients in this arm received bevacizumab monotherapy up to a total duration of 1 year (treatment period 2). At the end of treatment (i.e., after approximately 55 weeks), patients were followed up until the end of the study.	Chemotherapy Participants randomized to receive chemotherapy alone. For patients randomized to the chemotherapy alone arm, investigators could select from one of three chemotherapy regimens. After completing chemotherapy (treatment period 1) patients entered a post-treatment surveillance period for the remainder of the first year after randomization (treatment period 2). At the end of treatment (i.e., after approximately 55 weeks), patients were followed up until the end of the study.
Overall Study Death	4	5
Overall Study Breast Cancer Recurrence/2nd Primary	30	60
Overall Study Adverse Event/Intermittent Illness	255	29
Overall Study Violation Criteria at Entry	3	17
Overall Study Withdrew Consent	59	55
Overall Study Refused Treatment/Did Not Cooperate	52	42
Overall Study Failure to Return	1	4
Overall Study Other Protocol Violation	5	21
Overall Study Administrative/Other	22	75

Baseline Characteristics

BEATRICE Study: A Study of Bevacizumab (Avastin) Adjuvant Therapy in Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Total n=2591 Participants Total of all reporting groups
Age, Customized < 40 years	231 participants n=93 Participants	253 participants n=4 Participants	484 participants n=27 Participants
Age, Customized >= 40 to < 65 years	952 participants n=93 Participants	916 participants n=4 Participants	1868 participants n=27 Participants
Age, Customized >= 65 years	118 participants n=93 Participants	121 participants n=4 Participants	239 participants n=27 Participants
Sex: Female, Male Female	1301 Participants n=93 Participants	1290 Participants n=4 Participants	2591 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Time to Invasive Disease-free Survival (IDFS) Event	NA Months The median was not reached.	NA Months The median was not reached.	—	—

PRIMARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012 up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Percentage of Participants With Invasive Disease-free Survival (IDFS) Events Percentage of Participants with Events	14.5 Percentage of participants	15.9 Percentage of participants	—	—
Percentage of Participants With Invasive Disease-free Survival (IDFS) Events Percentage of Participants without Events	85.5 Percentage of participants	84.1 Percentage of participants	—	—

PRIMARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

IDFS, was a composite endpoint defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site); Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Time to Invasive Disease-free Survival (IDFS) Event Excluding Second Primary Non-Breast Invasive Cancer	NA Months The median was not reached.	NA Months The median was not reached.	—	—

PRIMARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

IDFS, was a composite endpoint defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site); Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer. Percentage of participants with and without IDFS Events by the time of data cutoff is presented.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Percentage of Participants With Invasive Disease-free Survival (IDFS) Events Excluding Second Primary Non-Breast Invasive Cancer Percentage of Participants with Events	13.5 Percentage of participants	14.7 Percentage of participants	—	—
Percentage of Participants With Invasive Disease-free Survival (IDFS) Events Excluding Second Primary Non-Breast Invasive Cancer Percentage of Participants without Events	86.5 Percentage of participants	85.3 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

OS was defined as the time from randomization to death attributable to any cause. Patients for whom no death is captured in the clinical database up to the clinical cut-off date are censored at the last time they were known to be alive.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Time to Overall Survival (OS) Event	NA Months The median was not reached	NA Months The median was not reached	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 30 June 2014: up to 77 months)

Population: Intent-to-treat population, defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Time to Overall Survival (OS) Event	NA Months The median was not estimable.	NA Months The median was not estimable.	—	—

SECONDARY outcome

Timeframe: Event driven (until data cut off: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Percentage of Participants With Overall Survival (OS) Event with events	7.1 percentage of participants	8.3 percentage of participants	—	—
Percentage of Participants With Overall Survival (OS) Event without events	92.9 percentage of participants	91.7 percentage of participants	—	—

SECONDARY outcome

Timeframe: Event driven (until data cut off: 30 June 2014: up to 77 months)

Population: Intent-to-treat population, defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Percentage of Participants With Overall Survival (OS) Event with events	11.1 percentage of participants	11.6 percentage of participants	—	—
Percentage of Participants With Overall Survival (OS) Event without events	88.9 percentage of participants	88.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat participants, defined as all randomized participants.

BCFI is defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral local/regional invasive breast cancer recurrence or distant breast cancer recurrence; Contralateral invasive breast cancer; Ipsilateral or contralateral Ductal carcinoma in situ or Death only from breast cancer cause.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Time to Breast Cancer-Free Interval (BCFI) Event	NA Months The median was not reached.	NA Months The median was not reached.	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

BCFI is defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral local/regional invasive breast cancer recurrence or distant breast cancer recurrence; Contralateral invasive breast cancer; Ipsilateral or contralateral DCIS or Death only from breast cancer cause. Percentage of participants with and without BCFI events by the time of the data cutoff is presented.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Percentage of Participants With Breast Cancer-Free Interval (BCFI) Events Percentage of Participants with Events	13.2 Percentage of participants	14.2 Percentage of participants	—	—
Percentage of Participants With Breast Cancer-Free Interval (BCFI) Events Percentage of Participants without Events	86.8 Percentage of participants	85.8 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

DFS is defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site); Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer, Second primary non-breast invasive cancer or New diagnosis of an ipsilateral or contralateral Ductal carcinoma in situ (DCIS).

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Time to Disease-Free Survival (DFS) Event	NA Months The median was not reached.	NA Months The median was not reached.	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Percentage of Participants With Disease-Free Survival (DFS) Events with Events	14.7 Percentage of participants	16.1 Percentage of participants	—	—
Percentage of Participants With Disease-Free Survival (DFS) Events without Events	85.3 Percentage of participants	83.9 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

DDFS is defined as the time from randomization until the date of the first occurrence of one of the following events: Distant recurrence; Death attributable to any cause; Second primary non-breast invasive cancer (with the exception of non-melanoma Skin cancers).

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Time to Distant Disease-Free Survival (DDFS) Event	NA Months The median was not reached.	NA Months The median was not reached	—	—

SECONDARY outcome

Timeframe: Event driven (until data cutoff: 29 February 2012: up to 49 months)

Population: Intent-to-treat population, defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1301 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1290 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Percentage of Participants with Events	11.7 Percentage of participants	12.7 Percentage of participants	—	—
Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Percentage of Participants without Events	88.3 Percentage of participants	87.3 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Through end of study: 30 June 2014: up to 77 months

Population: Safety population, defined as all randomized participants who received at least one dose of study drug. Participants who received at least one full or partial dose of bevacizumab were included in the bevacizumab and chemotherapy arm; all other patients were analyzed in the chemotherapy arm.

An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is Life-Threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	Bevacizumab and Chemotherapy n=1288 Participants Participants randomized to receive bevacizumab and chemotherapy	Chemotherapy n=1271 Participants Participants randomized to receive chemotherapy alone	Bevacizumab and Chemotherapy (>18 Months) n=1288 Participants Occurring in participants who received bevacizumab and chemotherapy, more than 18 months after first dose	Chemotherapy (>18 Months) n=1271 Participants Occurring in participants who received chemotherapy alone, more than 18 months after first dose
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and Deaths Serious Adverse Events	379 Participants	250 Participants	45 Participants	48 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and Deaths Adverse Events (5% Reporting Threshold)	1268 Participants	1233 Participants	0 Participants	0 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and Deaths Deaths	31 Participants	41 Participants	113 Participants	106 Participants

Adverse Events

Bevacizumab and Chemotherapy (0-18 Months)

Serious events: 379 serious events

Other events: 1268 other events

Deaths: 0 deaths

Chemotherapy (0-18 Months)

Serious events: 250 serious events

Other events: 1233 other events

Deaths: 0 deaths

Bevacizumab and Chemotherapy (>18 Months)

Serious events: 45 serious events

Other events: 0 other events

Deaths: 0 deaths

Chemotherapy (>18 Months)

Serious events: 48 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

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