title: Sorafenib  in locally advanced or metastatic breast cancer.
abstract: BACKGROUND
  Sorafenib is an oral multikinase inhibitor with anti-angiogenic and anti-proliferative activity that is indicated for use in hepatocellular and renal cell carcinomas. Sorafenib is being developed in a number of solid tumors, including breast cancer (BC).
  
  
  METHODS
  A series of four randomized, double-blind, placebo-controlled Phase IIb screening Trials were developed to Investigate the Efficacy of Sorafenib (TIES) when added to select chemotherapies for patients with HER2-negative advanced BC with a primary endpoint of progression-free survival (PFS). Results have been varied. SOLTI-0701 reported significant PFS benefit for sorafenib plus capecitabine as first- or second-line treatment, and AC01B07 reported a modest but significant PFS benefit when sorafenib was combined with gemcitabine or capecitabine for patients whose disease had progressed during or after bevacizumab. Sorafenib plus first-line paclitaxel did not significantly improve PFS (NU07B1 study), nor did its addition to first-line docetaxel and/or letrozole (FM-B07-01 study). A Phase III trial of sorafenib plus capecitabine has been initiated.
  
  
  CONCLUSIONS
  Phase IIb data indicate a potential role for sorafenib in combination with select chemotherapies for HER2-negative advanced BC, but Phase III confirmatory trials are necessary. The variability in results across studies with sorafenib may be related to the chemotherapy combination and/or patient population.
authors.affiliation: Maggie Daley Center for Women's Cancer Care, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N St Clair St, Suite 850, Chicago, IL 60611, USA. WGradishar@nmff.org
authors.forename: William J
authors.initials: WJ
authors.lastname: Gradishar
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077289:Letrozole; D009536:Niacinamide / Q000031:analogs & derivatives; D009570:Nitriles / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D000077157:Sorafenib; D043823:Taxoids / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; D000068258:Bevacizumab; D000069287:Capecitabine; D003841:Deoxycytidine; D000077143:Docetaxel; D005472:Fluorouracil; D000077289:Letrozole; D009536:Niacinamide; D009570:Nitriles; D017239:Paclitaxel; D010671:Phenylurea Compounds; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077157:Sorafenib; D043823:Taxoids; D014230:Triazoles; D000093542:Gemcitabine