Trial Outcomes & Findings for A Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (AMBER) (NCT NCT00473590)

Last Updated: 2017-06-14

Results Overview

Progression-free survival (PFS) was defined as the time from randomization to disease progression or death on study from any cause within 30 days of the last response assessment. Disease progression was determined by the investigator using the International Myeloma Working Group's (IMWG) uniform response criteria. Median PFS was estimated using Kaplan-Meier methodology. For patients who were alive at the time of the analysis and whose disease had not yet progressed, PFS was censored at the time of the last response assessment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

102 participants

Primary outcome timeframe

From randomization to disease progression or death on study (up to 116 weeks).

Results posted on

2017-06-14

Participant Flow

Phase II, randomized, blinded, placebo-controlled, multicenter study designed to provide a preliminary assessment of the safety and efficacy of combining bevacizumab with bortezomib in patients with relapsed or refractory multiple myeloma starting 11 July 2007 and completing 9 November 2009.

Participant milestones

Participant milestones
Measure	BORT + P Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Overall Study STARTED	53	49
Overall Study Treated	52	48
Overall Study Safety Population	50	50
Overall Study COMPLETED	8	11
Overall Study NOT COMPLETED	45	38

Reasons for withdrawal

Reasons for withdrawal
Measure	BORT + P Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Overall Study Adverse Event	3	3
Overall Study Death	4	2
Overall Study Progression not resulting in death	24	20
Overall Study Non-protocol-specified therapy	7	5
Overall Study Physician Decision	2	4
Overall Study Withdrawal by Subject	5	3
Overall Study Other	0	1

Baseline Characteristics

A Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (AMBER)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BORT + P n=53 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=49 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.	Total n=102 Participants Total of all reporting groups
Age, Continuous	64.9 years STANDARD_DEVIATION 9.2 • n=5 Participants	65.6 years STANDARD_DEVIATION 9.3 • n=7 Participants	65.2 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	20 Participants n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	29 Participants n=7 Participants	59 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to disease progression or death on study (up to 116 weeks).

Population: Randomized Patients

Outcome measures

Outcome measures
Measure	BORT + P n=53 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=49 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Progression-free Survival (PFS)	5.1 months Interval 4.17 to 7.2	6.2 months Interval 4.4 to 8.54

SECONDARY outcome

Timeframe: From randomization to the end of study (clinical cut-off; up to 116 weeks).

Population: Randomized Patients

Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR, respectively) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the International Myeloma Working Group's (IMWG's) uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.

Outcome measures

Outcome measures
Measure	BORT + P n=53 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=49 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Number of Participants With an Overall Response	23 participants	25 participants

SECONDARY outcome

Timeframe: From randomization to the end of study (clinical cut-off; up to 116 weeks).

Population: Randomized Patients

Overall response was defined as a stringent complete response, complete response, very good partial response, or partial response (sCR, CR, VGPR, and PR) determined on two consecutive assessments ≤ 6 weeks apart and before the initiation of any new anti-tumor therapy, as assessed by the investigator using the IMWG's uniform response criteria. Patients without a post-baseline response assessment or who died prior to their first scheduled response assessment were considered non-responders.

Outcome measures

Outcome measures
Measure	BORT + P n=53 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=49 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Percentage of Participants With an Overall Response	43.4 Percentage of Participants Interval 30.1 to 57.7	51.0 Percentage of Participants Interval 36.3 to 65.2

SECONDARY outcome

Timeframe: From randomization to the end of study (clinical cut-off; up to 116 weeks).

Population: Randomized Patients with an overall response

Duration of response was defined as the time from the initial response to disease progression or death on study. Disease progression was determined by the investigator using the IMWG's uniform response criteria and defined as an increase of ≥25% from best response in: Serum M-protein and/or Urine M-protein and/or Marrow plasma cells; or new or increased plasmacytomas or bone lesions; or hypercalcemia due to myeloma. Duration of response was estimated using Kaplan-Meier. For patients who had not progressed or died, duration of response was censored at the date of the last response assessment.

Outcome measures

Outcome measures
Measure	BORT + P n=23 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=25 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Duration of Response	6.0 Months Interval 4.86 to 8.31	6.9 Months Interval 4.73 to 11.83

SECONDARY outcome

Timeframe: From randomization until death from any cause, up until the end of study (clinical cut-off; up to 116 weeks).

Population: Randomized Patients

Overall survival was defined as the duration of time from randomization until death from any cause. All deaths were included, whether they occurred on study treatment or following treatment discontinuation. Overall survival was estimated using Kaplan-Meier. For patients who had not died, overall survival was censored at the date that the patient was last known to be alive.

Outcome measures

Outcome measures
Measure	BORT + P n=53 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=49 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Overall Survival (OS)	24.0 Months Interval 15.24 to Upper limit of 95% CI not estimable due to too few events at the time of analysis.	NA Months The median duration of overall survival in the BORT + BV arm was not estimable, as too few events had been observed

SECONDARY outcome

Timeframe: Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination (up to 122 weeks).

Population: Safety population: all patients who were randomized and received any amount of study treatment. Two patients who randomized to the BORT + P arm received at least 1 dose of bevacizumab and were analyzed as bevacizumab-treated patients. Therefore, the safety analysis included 50 patients in the BORT + P arm and 50 patients in the BORT + BV arm.

Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. All serious adverse events are listed in the Adverse Event Reporting section.

Outcome measures

Outcome measures
Measure	BORT + P n=50 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=50 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Number of Participants With Selected Adverse Events (AEs) Arterial thromboembolic events (any grade)	0 Participants	1 Participants
Number of Participants With Selected Adverse Events (AEs) Bleeding other than pulmonary or CNS (Grade >=3)	1 Participants	2 Participants
Number of Participants With Selected Adverse Events (AEs) Febrile neutropenia (any grade)	1 Participants	1 Participants
Number of Participants With Selected Adverse Events (AEs) Gastrointestinal Perforation (Any Grade)	1 Participants	0 Participants
Number of Participants With Selected Adverse Events (AEs) Hypertension (Grade >= 3)	0 Participants	8 Participants
Number of Participants With Selected Adverse Events (AEs) Left Ventricular Systolic Dysfunction (Grade >= 3)	1 Participants	0 Participants
Number of Participants With Selected Adverse Events (AEs) Neutropenia (Grade >= 3)	6 Participants	10 Participants
Number of Participants With Selected Adverse Events (AEs) Osteonecrosis of the Jaw	0 Participants	1 Participants
Number of Participants With Selected Adverse Events (AEs) Peripheral Neuropathy (Grade >= 3)	7 Participants	8 Participants
Number of Participants With Selected Adverse Events (AEs) Pulmonary and CNS Bleeding (Any Grade)	0 Participants	1 Participants
Number of Participants With Selected Adverse Events (AEs) Thrombocytopenia (Grade >= 3)	15 Participants	15 Participants
Number of Participants With Selected Adverse Events (AEs) Vernous Thromboembolic Events (Grade >=3)	1 Participants	0 Participants

Adverse Events

BORT + P

Serious events: 26 serious events

Other events: 41 other events

Deaths: 0 deaths

BORT + BV

Serious events: 24 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	BORT + P n=50 participants at risk Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.	BORT + BV n=50 participants at risk Participants received bortezomib 1.3 mg/m\^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
Blood and lymphatic system disorders Anaemia	12.0% 6/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	18.0% 9/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Blood and lymphatic system disorders Neutropenia	12.0% 6/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	18.0% 9/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	32.0% 16/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	28.0% 14/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Gastrointestinal disorders Diarrhoea	10.0% 5/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	8.0% 4/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
General disorders Fatigue	6.0% 3/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	12.0% 6/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Nervous system disorders Neuralgia	12.0% 6/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	20.0% 10/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Nervous system disorders Neuropathy Peripheral	16.0% 8/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	16.0% 8/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Vascular disorders Hypertension	4.0% 2/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	20.0% 10/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
General disorders Pyrexia	6.0% 3/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	6.0% 3/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Infections and infestations Upper Respiratory Tract Infection	10.0% 5/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	12.0% 6/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Infections and infestations Urinary Tract Infection	6.0% 3/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	4.0% 2/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Nervous system disorders Headache	0.00% 0/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	8.0% 4/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	6.0% 3/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.
Skin and subcutaneous tissue disorders Rash	4.0% 2/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.	8.0% 4/50 • Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. Two patients who were randomized to the BORT + P arm received at least one dose of bevacizumab during the study and were analyzed as bevacizumab-treated patients. Therefore, 50 patients in the BORT + P arm and 50 patients were included in the BORT + BV arm in the safety analysis.

Additional Information

Medical Communications

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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.
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