Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer

HER2-negative participants administered

• doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
• docetaxel (T) + bevacizumab for 4 cycles followed by
• bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• doxorubicin 60 mg/m^2 IV push or infusion followed by cyclophosphamide 600 mg/m^2 IV push or infusion
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

• Avastin® (bevacizumab)
• Adriamycin® (doxorubicin)

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• docetaxel 100 mg/m^2 IV
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Note: The starting dose of docetaxel was reduced to 75 mg/m^2 if toxicity occurred that met the criteria for doxorubicin dose reduction

• Avastin® (bevacizumab)
• Taxotere® (docetaxel)

- bevacizumab 15 mg/kg was infused IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

• Avastin® (bevacizumab)

HER2-negative participants administered

• docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
• bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed

- bevacizumab 15 mg/kg was infused IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

• Avastin® (bevacizumab)

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• doxorubicin 50 mg/m^2 IV push or infusion followed by cyclophosphamide 500 mg/m^2 IV push or infusion followed by docetaxel 75 mg/m^2
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

• Avastin® (bevacizumab)
• Taxotere® (docetaxel)

All HER2-positive participants administered

• docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
• bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• docetaxel in 75 mg/m^2 IV followed by carboplatin AUC 6 mg/mL/min IV followed by
• trastuzumab 6 mg/kg by IV infusion (For the first cycle 1 only a loading dose of trastuzumab 8 mg/kg IV was infused on Day 2)
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

• Avastin® (bevacizumab)
• Taxotere® (docetaxel)
• Herceptin® (trastuzumab)

• bevacizumab 15 mg/kg was infused IV followed by
• trastuzumab 6 mg/kg IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

• Avastin® (bevacizumab)
• Herceptin® (trastuzumab)

Participants were evaluated for clinical CHF every 3 weeks during chemotherapy, every 3 months while on maintenance therapy, and every 3 months during the 2-year follow-up period. Left ventricular ejection fraction (LVEF) of CHF was assessed by multi-gated acquisition (MUGA) or echocardiogram (ECHO) performed midway through completion of chemotherapy according to a treatment-specific schedule, every 12 weeks during maintenance therapy, and at 6 and 24 months after completion of maintenance therapy.

Grade 3-4 CHF were identified through a clinical review of all study collected investigator verbatim and the Medical Dictionary for Regulatory Activities (MedDRA). The preferred terms (PT) cardiac failure congestive, cardiomyopathy, and ejection fraction decreased were associated with CHF.

An adverse event was any untoward medical occurrence in a participant of the clinical investigation, regardless of the relationship to study treatment.

A serious adverse event (SAE) was an AE that at any dose (including overdose) resulted in death, was life-threatening, required inpatient hospitalization or prolonged existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect, and/or was medically important.

Treatment-emergent adverse events (TEAE) were defined as AEs that developed or worsened in severity during the on-treatment period.

DFS was defined as the time from the administration of the first-dose of study medication until recurrence of tumor or death from any cause in the absence of previous documentation of tumor recurrence. DFS rate was the probability of being disease free and alive at a particular time. DFS rates were estimated using Kaplan-Meier Method, and 95% confidence intervals were computed using the method of Kalbfleisch and Prentice.

For participants who did have objective recurrence of tumor and who were still on study at the time of an analysis, or who were given antitumor treatment other than the study treatment, or who were removed from study follow-up prior to documentation of the tumor recurrence, DFS was censored at the last date the participant was known to be disease-free.