title: Cardiac safety results from a phase II, open-label, multicenter, pilot study of two docetaxel-based regimens plus bevacizumab for the adjuvant treatment of subjects with node-positive or high-risk node-negative breast cancer.
abstract: OBJECTIVE
  Adding antiangiogenic therapy to standard chemotherapy has improved response rates and progression-free survival in metastatic breast cancer (BC) patients. This phase II study evaluated cardiac safety of bevacizumab with/without trastuzumab with two docetaxel-based regimens in early BC.
  
  
  METHODS
  127 women with non-metastatic node-positive or high-risk node-negative BC were enrolled. Women with human epidermal growth factor receptor 2 (HER2)-negative BC (n = 93) received docetaxel/doxorubicin/cyclophosphamide (TAC) + bevacizumab, while women with HER2-positive disease (n = 34) received docetaxel/carboplatin/trastuzumab (TCH) + bevacizumab, every 3 weeks for six cycles. Maintenance therapy with bevacizumab alone or bevacizumab plus trastuzumab, respectively, was given every 3 weeks for 52 weeks. The primary objective was to evaluate cardiac safety, as measured by the incidence of ≥ grade 3 clinical congestive heart failure (CHF); the secondary objective was assessment of safety and toxicity.
  
  
  RESULTS
  At least one cardiac adverse event (AE; CHF, cardiomyopathy, or left ventricular dysfunction) was reported in 26.1% of TAC (n = 92) and 17.6% of TCH subjects (n = 34); there were no cardiac deaths. ≥ Grade 3 clinical CHF was observed in 4.3% in the TAC plus bevacizumab stratum and 0% in the TCH plus bevacizumab stratum. A ≥ grade 3 treatment-emergent AE (any kind) related to study treatment was observed in 59.8% in the TAC with bevacizumab and 52.9% in the TCH plus bevacizumab stratum.
  
  
  CONCLUSIONS
  Adding bevacizumab to a docetaxel-based regimen with trastuzumab did not appear to increase cardiotoxicity.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00446030, registered March 8, 2007.
authors.affiliation: University of California, Los Angeles, 10945 Le Conte Avenue, PVUB Suite 3360, Los Angeles, CA 90095 USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Hurvitz
authors.affiliation: Wilshire Oncology Medical Group, Inc., La Verne, CA USA.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Bosserman
authors.affiliation: Torrance Memorial Hospital, Redondo Beach, CA USA.
authors.forename: David
authors.initials: D
authors.lastname: Chan
authors.affiliation: Suburban Hematology and Oncology, Lawrenceville, GA USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Hagenstad
authors.affiliation: Cancer Center of Santa Barbara, Santa Barbara, CA USA.
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Kass
authors.affiliation: Georgetown University School of Medicine, Washington, DC USA.
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Smith
authors.affiliation: South Texas Oncology and Hematology, P.A., San Antonio, TX USA.
authors.forename: Gladys I
authors.initials: GI
authors.lastname: Rodriguez
authors.affiliation: sanofi U.S., Bridgewater, NJ USA.
authors.forename: Barrett H
authors.initials: BH
authors.lastname: Childs
authors.affiliation: University of California, Los Angeles, 10945 Le Conte Avenue, PVUB Suite 3360, Los Angeles, CA 90095 USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
keywords: Adverse events; Anthracyclines; Antiangiogenic; Congestive heart failure; Trastuzumab