title: Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study.
abstract: BACKGROUND
  Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma.
  
  
  METHODS
  Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC.
  
  
  RESULTS
  Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA.
  
  
  CONCLUSIONS
  In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turino, Orbassano, Italy. Electronic address: giorgio.scagliotti@unito.it.
authors.forename: Giorgio Vittorio
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: Department of Oncology, McGill University Health Centre, Montreal, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.affiliation: The Falck Division of Medical Oncology, Department of Oncology, Ospedale Niguarda Ca' Granada, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.affiliation: Joan Karnell Cancer Center, Pennsylvania Hospital, Philadelphia, Pennsylvania.
authors.forename: David H
authors.initials: DH
authors.lastname: Henry
authors.affiliation: Department of Oncology, Weston Park Hospital, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Penella J
authors.initials: PJ
authors.lastname: Woll
authors.affiliation: Department of Surgery, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Manegold
authors.affiliation: Centre Jean Bernard, Clinique Victor Hugo, Le Mans, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Solal-Celigny
authors.affiliation: South Texas Oncology and Hematology, San Antonio, Texas.
authors.forename: Gladys
authors.initials: G
authors.lastname: Rodriguez
authors.affiliation: The Maria Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.affiliation: Oncology Hematology Associates of Northern Illinois, Gurnee, Illinois.
authors.forename: Nilesh D
authors.initials: ND
authors.lastname: Mehta
authors.affiliation: Department of Medical Oncology, Western Hospital, Footscray, Victoria, Australia.
authors.forename: Lara
authors.initials: L
authors.lastname: Lipton
authors.affiliation: Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: José Angel
authors.initials: JA
authors.lastname: García-Sáenz
authors.affiliation: Instituto do Cancer Arnaldo Vieira de Carvalho, University of São Paulo Medical School, Sao Paolo, Brazil.
authors.forename: José Rodrigues
authors.initials: JR
authors.lastname: Pereira
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
authors.forename: Kumar
authors.initials: K
authors.lastname: Prabhash
authors.affiliation: Institutul Oncologic I. Chiricuta, Cluj-Napoca, Romania.
authors.forename: Tudor-Eliade
authors.initials: TE
authors.lastname: Ciuleanu
authors.affiliation: Regional Oncology Dispensary with Inpatient Sector, Plovdiv, Bulgaria.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kanarev
authors.affiliation: Global Biostatistical Sciences, Amgen Inc., Thousand Oaks, California.
authors.forename: Huei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Clinical Development, Amgen Inc., Thousand Oaks, California.
authors.forename: Arun
authors.initials: A
authors.lastname: Balakumaran
authors.affiliation: Clinical Development, Amgen Inc., Thousand Oaks, California.
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobs
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007390:International Agencies; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053245:RANK Ligand; D000069448:Denosumab; D000077211:Zoledronic Acid