Ramucirumab With Eribulin Versus Eribulin in Locally Recurrent or Metastatic Breast Cancer Previously Treated With Anthracycline and Taxane Therapy: A Multicenter, Randomized, Phase II Study

Clin Breast Cancer. 2016 Dec;16(6):471-479.e1. doi: 10.1016/j.clbc.2016.07.005. Epub 2016 Jul 29.

Abstract

Background: Use of antiangiogenic agents in treatment of metastatic breast cancer (MBC) remains controversial. We evaluated the efficacy and safety of ramucirumab and eribulin versus eribulin alone as third- to fifth-line therapy in women with advanced breast cancer.

Patients and methods: In this randomized (1:1), open-label, phase II study, US women aged 18 years or older with 2 to 4 previous chemotherapy regimens for locally recurrent or MBC, previous anthracycline and taxane treatment, and Eastern Cooperative Oncology Group performance status of 0 or 1 received ramucirumab with eribulin or eribulin alone in 21-day cycles (eribulin 1.4 mg/m2 intravenously on days 1 and 8; ramucirumab 10 mg/kg intravenously on day 1). Randomization was stratified according to previous antiangiogenic therapy and triple-negative status. The primary end point was progression-free survival (PFS) in the intention to treat population.

Results: One hundred forty-one women were randomized to ramucirumab with eribulin (n = 71) or eribulin alone (n = 70). Median PFS for ramucirumab with eribulin was 4.4 months (95% confidence interval [CI], 3.1-6.7) compared with 4.1 months (95% CI, 3.2-5.6) for eribulin (hazard ratio [HR], 0.83; 95% CI, 0.56-1.23; P = .35). Median overall survival in patients who received ramucirumab with eribulin was 13.5 months (95% CI, 10.4-17.9) compared with 11.5 months (95% CI, 9.0-17.3) in patients who received eribulin alone (HR, 0.91; 95% CI, 0.59-1.41; P = .68); objective response rate was 21% (13 of 62 patients) for the combination and 28% (17 of 60 patients) for eribulin alone. No unexpected toxicity was identified for the combination.

Conclusion: Ramucirumab combined with eribulin did not significantly improve PFS in advanced MBC.

Keywords: Antiangiogenic therapy; Brain metastasis; Targeted agents; Triple-negative status; VEGFR-2.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Anthracyclines / therapeutic use
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Furans / administration & dosage
  • Furans / adverse effects
  • Furans / therapeutic use
  • Humans
  • Ketones / administration & dosage
  • Ketones / adverse effects
  • Ketones / therapeutic use
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Ramucirumab
  • Survival Analysis
  • Taxoids / therapeutic use
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Anthracyclines
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Furans
  • Ketones
  • Taxoids
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • eribulin