title: RANK ligand blockade with denosumab in combination with sorafenib in chemorefractory osteosarcoma: a possible step forward?
abstract: BACKGROUND
  There is no established systemic treatment option for unresectable osteosarcoma progressing after standard chemotherapy. A recently published clinical trial has demonstrated some activity of sorafenib in this situation. Preclinical research suggests a role for the inhibition of the receptor activator of nuclear factor-ĸB ligand (RANKL), but no clinical data have been reported so far.
  
  
  METHODS
  A 37-year-old man was diagnosed with unresectable osteoblastic, osteoblastoma-like osteosarcoma in the C7/Th1 vertebra. The tumour progressed locally despite two lines of chemotherapy and stereotactic radiotherapy. On treatment with sorafenib and denosumab, a complete metabolic remission was achieved and is ongoing for over 18 months. Immunohistochemistry revealed an overexpression of RANK and RANKL in the patient's primary tumour.
  
  
  CONCLUSIONS
  This is the first report of activity achieved by the combination of the tyrosine kinase inhibitor sorafenib and the RANKL inhibitor denosumab in a patient with osteosarcoma. It confirms preclinical data on RANK/RANKL inhibition in osteosarcoma and could serve as a hypothesis-generating approach for clinical trials in this patient population.
authors.affiliation: Division of Oncology/Haematology, Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Cathomas
authors.forename: Christian
authors.initials: C
authors.lastname: Rothermundt
authors.forename: Beata
authors.initials: B
authors.lastname: Bode
authors.forename: Bruno
authors.initials: B
authors.lastname: Fuchs
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
authors.forename: Michael
authors.initials: M
authors.lastname: Schwitter
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069448:Denosumab; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D012074:Remission Induction; D016879:Salvage Therapy; D000077157:Sorafenib
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010671:Phenylurea Compounds; D053245:RANK Ligand; D009536:Niacinamide; D000069448:Denosumab; D000077157:Sorafenib