title: Addition of bevacizumab to three docetaxel regimens as adjuvant therapy for early stage breast cancer.
abstract: Docetaxel-containing chemotherapy improves disease-free survival (DFS) and overall survival in patients with early stage breast cancer. Bevacizumab improves response rate and DFS in metastatic breast cancer. However, adding antivascular endothelial growth factor therapy to anthracycline-containing chemotherapy may increase cardiotoxicity. This trial evaluates the feasibility of adding bevacizumab to three standard adjuvant docetaxel regimens with a primary endpoint of grade ≥3 congestive heart failure (CHF). Phase IIb, randomized, non-comparative study of women with previously untreated node-positive or high-risk node-negative breast cancer. Human epidermal growth factor receptor 2 (HER2)-negative patients were randomized to: (arm A) doxorubicin + cyclophosphamide followed by docetaxel or (arm B) docetaxel + doxorubicin + cyclophosphamide. HER2-positive patients (arm C) received docetaxel + carboplatin + trastuzumab for 52 weeks. All patients received bevacizumab beginning on day 1 for 52 weeks. Safety data in 212 women (mean age = 53.1 years) show that 1 patient each in arm A (1.3 %) and arm C (1.7 %), and 3 patients in arm B (4.0 %) experienced clinical CHF grade ≥3. A decreased ejection fraction was observed in 1 patient each in arms A and C, and cardiac disorder was observed in 12.8, 22.7, and 8.5 % in arms A, B, and C, respectively. A grade 3/4 treatment-emergent adverse event was reported in 82.1, 84.0, and 52.5 % of participants in arms A, B, and C, respectively. Kaplan-Meier estimates of DFS show rates at 24 months of 85.5, 90.4, and 90.4 % in arms A, B, and C, respectively. Adding bevacizumab to three standard docetaxel-based chemotherapy regimens as adjuvant treatment in patients with node-positive and high-risk node-negative breast cancer resulted in a low rate of clinical CHF grade ≥3. Maintenance bevacizumab monotherapy did not identify any new safety signals. Breast cancer recurrence/relapse, secondary malignancies, and death were uncommon, although the follow-up time in this study was relatively short.
authors.affiliation: Sarah Cannon Research Institute, Tennessee Oncology, PLLC, 250 25th Avenue North, Suite 100, Nashville, TN, 37203, USA, dyardley@tnonc.com.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Lowell
authors.initials: L
authors.lastname: Hart
authors.forename: David
authors.initials: D
authors.lastname: Waterhouse
authors.forename: Robert
authors.initials: R
authors.lastname: Whorf
authors.forename: D Randolph
authors.initials: DR
authors.lastname: Drosick
authors.forename: Patrick
authors.initials: P
authors.lastname: Murphy
authors.forename: Suprith
authors.initials: S
authors.lastname: Badarinath
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Daniel
authors.forename: Barrett H
authors.initials: BH
authors.lastname: Childs
authors.forename: Howard
authors.initials: H
authors.lastname: Burris
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab