SABRE-B: an evaluation of paclitaxel and bevacizumab with or without sunitinib as first-line treatment of metastatic breast cancer.
BACKGROUND
The vascular endothelial growth factor (VEGF) pathway can be targeted through VEGF neutralization or VEGF receptor (VEGFR) blockade using tyrosine kinase inhibition. Because laboratory models suggest that combining these approaches might be synergistic, we sought to evaluate the feasibility and efficacy of combining sunitinib with paclitaxel + bevacizumab (PB).


METHODS
Patients with human epidermal growth factor receptor 2 (HER2)-negative, metastatic breast cancer receiving first-line chemotherapy were randomized to PB or PB with sunitinib (PBS), with planned escalation of the sunitinib dose.


RESULTS
Forty-six patients were randomized to PB or PBS with sunitinib dosed at 25 mg p.o. daily. Patients receiving PBS encountered substantial toxicity that precluded adequate treatment. The percentage of patients with grade ≥3 adverse events was greater in the PBS arm than the PB arm (83% versus 57%), and sunitinib dosing was modified in 78% of patients, most often due to neutropenia, febrile neutropenia, and fatigue. In addition, 44% of patients had sunitinib dose reduction to 12.5 mg, and 39% required discontinuation. Patients receiving PBS had more bevacizumab treatment interruptions and discontinuations because of toxicity. Median treatment duration was longer in the PB arm compared with the PBS arm (14.1 versus 11.1 weeks), reflecting early treatment discontinuation of PBS. Because of poor tolerability of the addition of sunitinib to PB, the planned sunitinib dose escalation was halted and the study accrual was terminated.


CONCLUSIONS
Adding sunitinib to standard doses of bevacizumab plus paclitaxel for metastatic breast cancer is not feasible. Different strategies will be required to evaluate whether there is additional clinical benefit to combining VEGF/VEGFR-targeted agents.
Mayer
E L
EL
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA. Electronic address: emayer@partners.org.
Dhakil
S
S
Department of Oncology and Internal Medicine, Cancer Center of Kansas, Wichita, KS.
Patel
T
T
Department of Oncology and Internal Medicine, The Mark H. Zangmeister Center, Columbus, OH.
Sundaram
S
S
Sharp Healthcare, San Diego, CA.
Fabian
C
C
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS.
Kozloff
M
M
Department of Oncology, Ingalls Memorial Hospital, Harvey IL.
Qamar
R
R
Oncology Alliance, Glendale WI.
Volterra
F
F
Department of Medicine (Oncology), Eastchester Cancer Care, Bronx, NY.
Parmar
H
H
Department of Avastin BioOncolgy, Genentech, Inc., South San Francisco, CA.
Samant
M
M
Department of Biostatistics, Genentech, Inc., South San Francisco, CA, USA.
Burstein
H J
HJ
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D011758:Pyrroles; D000068258:Bevacizumab; D017239:Paclitaxel; D000077210:Sunitinib