A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01).
BACKGROUND
Addition of the antiangiogenic agent bevacizumab to paclitaxel significantly improves response rates and progression-free survival for metastatic breast cancer (MBC). To assess the activity of docetaxel plus bevacizumab, a multicenter phase II trial was conducted.


METHODS
Patients with measurable first-line HER2/neu-negative MBC were eligible. This trial began as a 2-arm study with a docetaxel-alone arm. When bevacizumab became widely available, it was converted to a 1-arm open-label trial of docetaxel/bevacizumab. Patients enrolled in the docetaxel-alone arm were permitted to cross over to docetaxel/bevacizumab. Patients received bevacizumab 15 mg/kg and docetaxel 75 mg/m2 intravenously (I.V.) every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal.


RESULTS
From March 2005 to September 2006, 76 patients were enrolled. Of the 7 patients who were randomized to docetaxel alone, 6 crossed over to docetaxel/bevacizumab (included in the safety analysis only). Two patients were found to be ineligible before receiving drug. Efficacy data are based on the 67 patients who were originally enrolled in the docetaxel/bevacizumab arm and received at least 1 dose of study medication. The confirmed objective response rate is 51% (34 of 67) with 9% complete responses (6 of 67) and 42% partial responses (28 of 67). Nine additional patients (13%) had stable disease lasting >or= 6 months. With a median follow-up of 21.7 months, the median time to progression is 9.3 months, and median overall survival is 26.3 months. Common grade 3/4 adverse events included neutropenia (33%), leukopenia/lymphopenia (25%), fatigue (22%), infection (17%), pain (16%), and hypertension (9%).


CONCLUSIONS
Docetaxel/bevacizumab was generally well tolerated with manageable toxicity and promising efficacy results.
Hurvitz
Sara A
SA
David Geffen School of Medicine, University of California, Los Angeles, CA, USA. shurvitz@mednet.ucla.edu
Allen
Heather J
HJ
Moroose
Rebecca L
RL
Chan
David
D
Hagenstad
Christopher
C
Applebaum
Steven H
SH
Patel
Giribala
G
Hu
Eddie H
EH
Ryba
Nancy
N
Lin
Lii-Shin
LS
Wang
Hejing
H
Glaspy
John
J
Slamon
Dennis J
DJ
Kabbinavar
Fairooz
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids