title: Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracyclines or taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336.
abstract: OBJECTIVE
  We conducted a cooperative group phase II study to assess antitumor activity and toxicity of sorafenib in patients with metastatic breast cancer (MBC) who had received prior treatment for their disease.
  
  
  METHODS
  Patients were eligible if they had measurable disease and had previously received an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. The primary end point of the study was tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). The study was designed in two stages. Sorafenib was administered as 400 mg twice daily on days 1 through 28 of each 4-week cycle.
  
  
  RESULTS
  Twenty-three patients were enrolled with a median age of 54 years (range, 37 to 70 years). Twenty-two (96%) had prior anthracycline treatment and 16 (70%) had prior taxane treatment. Patients received sorafenib for a median of two cycles (range, one to 15 cycles) with a median follow-up of 2.4 years (range, 2.2 to 2.6 years). There were no grade 4 toxicities and few grade 3 toxicities. Among the 20 patients eligible for efficacy analysis, no patients experienced a partial response or complete response per RECIST criteria. Thus, the trial stopped at the end of the first stage per study design. Two patients (10%; 90% CI, 1.8% to 28.3%) achieved stable disease lasting longer than 6 months.
  
  
  CONCLUSIONS
  Sorafenib as a single agent, although well tolerated, did not exhibit activity when measured by tumor shrinkage in patients with MBC who had received prior treatment. Further research should focus on combinations with standard therapy and end points more sensitive to effects of targeted agents, such as disease stabilization.
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic and Mayo Foundation, Jacksonville, FL 32224, USA. morenoaspitia.alvaro@mayo.edu
authors.forename: Alvaro
authors.initials: A
authors.lastname: Moreno-Aspitia
authors.forename: Roscoe F
authors.initials: RF
authors.lastname: Morton
authors.forename: David W
authors.initials: DW
authors.lastname: Hillman
authors.forename: Wilma L
authors.initials: WL
authors.lastname: Lingle
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: Martin
authors.initials: M
authors.lastname: Wiesenfeld
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Tom R
authors.initials: TR
authors.lastname: Fitch
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D043823:Taxoids; D009536:Niacinamide; D000077157:Sorafenib