Evidence map›Paper›PMID 25425475›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2015

Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events.

M R Smith, R E Coleman, L Klotz, K Pittman, P Milecki, S Ng, K N Chi, A Balakumaran, R Wei, H Wang and 2 more

Erratum issued Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT00321620 (A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid), which is not on this map. Cited by 71 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 4 pooled it
8.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00321620 phase3completednot on this map

A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa®) in the Treatment of Bone Metastases in Men With Hormone-Refractory Prostate Cancer

TypeinterventionalSponsorAmgenRan2006 to 2012Enrolled1,904ConditionsBone MetastasesArmszoledronic acid, denosumab
3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 4 syntheses or guidelines pooled it, 144 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2016
    Trial
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Management of bone metastasis in prostate cancer.Journal of bone and mineral metabolism · 2023
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 8 institutions in 5 countries.

M R SmithDepartment of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, USA smith.matthew@mgh.harvard.edu.
R E ColemanAcademic Unit of Clinical Oncology, Sheffield Cancer Research Centre, Sheffield, UK.
L KlotzDivision of Urology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada.
K PittmanDepartment of Medical Oncology, The Queen Elizabeth Hospital, Woodville, Australia.
P MileckiDepartment of Electroradiology, Poznan University of Medical Sciences, Poznan Department of Radiotherapy, Wielkopolskie Centrum Onkologii, Poznan, Poland.
S NgSt John of God Hospital, Subiaco, Australia.
K N ChiDepartment of Medical Oncology, BC Cancer Agency, Vancouver, Canada.
A BalakumaranDepartment of Hematology/Oncology.
R WeiGlobal Biostatistical Science, Amgen Inc., Thousand Oaks, USA.
H WangGlobal Biostatistical Science, Amgen Inc., Thousand Oaks, USA.
A BraunDepartment of Hematology/Oncology.
K FizaziDepartment of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Paris, France.
Amgen (United States) · USBC Cancer Agency · CACentrum Onkologii · PLHealth Sciences Centre · CAInstitut Gustave Roussy · FRMassachusetts General Hospital · USQueen Elizabeth Hospital · AUSt John of God Hospital · AU

Funding

Midcareer Investigator AwardK24CA121990 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SMITH, MATTHEW RAYMOND · 2007 to 2016
$1.9M
NCI NIH HHS K24 CA121990
6 · The paper itself

Abstract

backgroundIn a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point. PATIENTS AND

methodsPatients with CRPC, no previous bisphosphonate exposure, and radiographic evidence of bone metastasis were randomized to subcutaneous denosumab 120 mg plus i.v. placebo every 4 weeks (Q4W), or i.v. zoledronic acid 4 mg plus subcutaneous placebo Q4W during the blinded treatment phase. SSEs were defined as radiation to bone, symptomatic pathologic fracture, surgery to bone, or symptomatic spinal cord compression. The relationship between SSE or SRE and time to moderate/severe pain was assessed using the Brief Pain Inventory Short Form.

resultsTreatment with denosumab significantly reduced the risk of developing first SSE [HR, 0.78; 95% confidence interval (CI) 0.66-0.93; P = 0.005] and first and subsequent SSEs (rate ratio, 0.78; 95% CI 0.65-0.92; P = 0.004) compared with zoledronic acid. The treatment differences in the number of patients with SSEs or SREs were similar (n = 48 and n = 45, respectively). Among patients with no/mild pain at baseline, both SSEs and SREs were associated with moderate/severe pain development (P < 0.0001). Fewer patients had skeletal complications, particularly fractures, when defined as SSE versus SRE.

conclusionIn patients with CRPC and bone metastases, denosumab reduced the risk of skeletal complications versus zoledronic acid regardless of whether the end point was defined as SSE or SRE.

Indexed as

AgedBone Density Conservation AgentsBone NeoplasmsDenosumabDouble-Blind MethodHumansMaleMiddle AgedProstatic Neoplasms, Castration-ResistantBone Density Conservation AgentsDenosumabdenosumabphase IIIprostate cancerskeletal-related eventssymptomatic skeletal eventszoledronic acid

Identifiers

PMID25425475
PMCPMC4304378
OpenAlexW2153871840

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.