Trial Information

A Phase II Trial of Open-Label Bevacizumab Administered With Anastrozole or Fulvestrant as First-Line Therapy in Postmenopausal Hormone Receptor- Positive Metastatic Breast Cancer (With Trastuzumab in HER2-Positive Patients)

Regimen A: Bevacizumab/anastrozole (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg
IV every 2 weeks [patients who are also receiving trastuzumab have the option to receive
their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see
Trastuzumab section below)] and anastrozole (1 mg orally daily). Treatment will be given in
4-week cycles. Response assessments will be performed after 2 cycles. Patients who respond
to treatment or have stable disease will continue to be evaluated every 2 cycles. After 6
months, response assessment will occur every 3 months. A patient may remain on study if
radiation is deemed necessary and appropriate, provided that there are other sites of
measurable disease outside the field of radiation that may be followed. Treatment occurs
until disease progression. Patients will be selected for this treatment arm per the
following guidelines: >=12 months from adjuvant endocrine therapy OR >=12 months from
adjuvant aromatase inhibitors OR Endocrine therapy naive OR Prior tamoxifen exposure or
tamoxifen intolerance

Regimen B: Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg
IV every 2 weeks [patients who are also receiving trastuzumab have the option to receive
their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see
Trastuzumab section below)] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed
by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the
first day of all subsequent cycles thereafter, patients in this treatment arm will receive
250 mg intramuscularly of fulvestrant). Treatment will be given in 4-week cycles. Response
assessments will be performed after 2 cycles. Patients who respond to treatment or have
stable disease will continue to be evaluated every 2 cycles. After 6 months, response
assessment will occur every 3 months. A patient may remain on study if radiation is deemed
necessary and appropriate, provided that there are other sites of measurable disease outside
the field of radiation that may be followed. Treatment occurs until disease progression.
Patients will be selected for this treatment arm per the following guidelines: <12 months
from adjuvant aromatase inhibitor therapy OR Intolerant of aromatase inhibitors OR Disease
progression on adjuvant aromatase inhibitors OR Physician discretion

Trastuzumab: Patients in Treatment Arm A or Treatment Arm B who have FISH HER2+ or IHC3+
breast cancer will also receive treatment with trastuzumab in addition to their treatment
with the combination of bevacizumab with either anastrozole or fulvestrant. Trastuzumab will
be administered ONLY to patients with HER2+ breast cancer (FISH-positive or IHC3+). An 8
mg/kg loading dose of IV trastuzumab will be administered on Day 1, followed by doses of 6
mg/kg IV trastuzumab once every 3 weeks. These patients will have the option of receiving
their bevacizumab doses at 15 mg/kg every 3 weeks rather than 10 mg/kg every 2 weeks (if
they prefer to keep their bevacizumab dosing schedule consistent with their trastuzumab
dosing schedule so that the number of visits they must make to the study site is minimized).
The dosing schedules for anastrozole (for HER2+ patients in Treatment Arm A) and fulvestrant
(for HER2+ patients in Treatment Arm B) will not change.