A multicenter phase I-II study of docetaxel plus epirubicin plus bevacizumab as first-line treatment in women with HER2-negative metastatic breast cancer

Breast. 2013 Dec;22(6):1171-7. doi: 10.1016/j.breast.2013.08.017. Epub 2013 Oct 1.

Abstract

Purpose: To assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E) in combination with bevacizumab (B) [DEB regimen] as front-line treatment in patients with metastatic breast cancer (MBC).

Patients and methods: Women with previously untreated HER2-negative MBC received B (15 mg/kg), E (75 mg/m2) and D (75 mg/m2) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles followed by B (15 mg/kg q3w) until disease progression. Primary endpoint was the overall response rate (ORR). Circulating tumor cells (CTCs) were evaluated using the CellSearch system at different time points during therapy.

Results: Eighty-three women were enrolled with median age 62 years, performance status 0-1 in 93%, triple negative disease in 12% and liver metastases in 47%. In an intention to treat analysis, complete response was achieved in 13 (15.7%) and partial response in 42 (50.6%) (overall response rate 66.3%; 95% CI 56.09-76.44%). The median time to progression was 20.1 months and the 1-year overall survival rate 82.3%. Grade 3-4 neutropenia occurred in 37%, febrile neutropenia in 10%, anemia in 4%, thrombocytopenia in 2% and diarrhea in 2% of patients. There were two deaths possibly related to study treatment (sigmoid perforation n = 1; sudden death n = 1). Moreover, one patient developed pulmonary embolism and another one myocardial infarction while on treatment. Although DEB administration significantly reduced the proportion of patients presenting CTCs, the detection of ≥5 or ≥1 CTCs before treatment initiation was significantly associated with worse progression-free survival (p = 0.001 and p = 0.004) and overall survival (p = 0.001 and p = 0.027), respectively.

Conclusions: The DEB regimen is a very active but also potentially toxic combination in MBC. Detection of CTCs before treatment is associated with worse outcome.

Clinicaltrialsgov: NCT00705315.

Keywords: Bevacizumab; CTC; Docetaxel; Epirubicin; MBC.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Anemia / chemically induced
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Docetaxel
  • Epirubicin / administration & dosage
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / secondary*
  • Lung Neoplasms / secondary*
  • Middle Aged
  • Neoplastic Cells, Circulating
  • Neutropenia / chemically induced
  • Receptor, ErbB-2 / analysis
  • Survival Rate
  • Taxoids / administration & dosage
  • Thrombocytopenia / chemically induced
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Taxoids
  • Docetaxel
  • Bevacizumab
  • Epirubicin
  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT00705315