Evidence map›Paper›PMID 26335402›Full record

Trial reportSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer2016

Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer.

Alison T Stopeck, Karim Fizazi, Jean-Jacques Body, Janet E Brown, Michael Carducci, Ingo Diel, Yasuhiro Fujiwara, Miguel Martín, Alexander Paterson, Katia Tonkin and 9 more

Erratum issuedAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 88 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Prevalence of medication related osteonecrosis of the jaw in patients treated with sequential antiresorptive drugs: systematic review and meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021
    Pooled it
  2. Long-term impact of bone-modifying agents for the treatment of bone metastases: a systematic review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021
    Pooled it
  3. Osteoporosis Management in the Era of COVID-19.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020
    Guideline
  4. Pooled it
  5. Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2019
    Pooled it
  6. Pooled it
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  15. Review
  16. Trastuzumab deruxtecan in patients with bone metastases from HR+/HER2-low breast cancer: efficacy enhanced by denosumab.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025
    Review
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  18. Review
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  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Alison T StopeckUniversity of Arizona Cancer Center, Tucson, AZ, USA. Alison.Stopeck@stonybrookmedicine.edu.
Karim FizaziInstitut Gustave Roussy, University of Paris Sud, Villejuif, France.
Jean-Jacques BodyCentre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
Janet E BrownCancer Research UK Experimental Cancer Medicine Centres, St James's University Hospital, Leeds, UK.
Michael CarducciSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Ingo DielCenter for Comprehensive Gynecology Clinic, Mannheim, Germany.
Yasuhiro FujiwaraNational Cancer Center Hospital, Tokyo, Japan.
Miguel MartínInstituto de Investigación Sanitaria General Gregorio Marañón, Universidad Complutense, Madrid, Spain.
Alexander PatersonTom Baker Cancer Centre, Calgary, AB, Canada.
Katia TonkinCross Cancer Institute, Edmonton, AB, Canada.
Neal ShoreCarolina Urologic Research Center, Myrtle Beach, SC, USA.
Paul SieberLancaster Urology, Lancaster, PA, USA.
Frank KueppersUrology Associates, Christchurch, New Zealand.
Lawrence KarshThe Urology Center of Colorado, Denver, CO, USA.
Denise YardleySarah Cannon Research Institute, Nashville, TN, USA.
Huei WangAmgen Inc., Thousand Oaks, CA, USA.
Tapan ManiarAmgen Inc., Thousand Oaks, CA, USA.
Jorge ArellanoAmgen Inc., Thousand Oaks, CA, USA.
Ada BraunAmgen Inc., Thousand Oaks, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeZoledronic acid (ZA) or denosumab treatment reduces skeletal-related events; however, the safety of prolonged therapy has not been adequately studied. Here, we describe safety results of extended denosumab therapy in patients with bone metastases from the open-label extension phase of two phase 3 trials.

methodsPatients with metastatic breast or prostate cancer received subcutaneous denosumab 120 mg Q4W or intravenous ZA 4 mg Q4W in a double-blinded fashion. Denosumab demonstrated superior efficacy in the blinded treatment phase; thus, patients were offered open-label denosumab for up to an additional 2 years.

resultsCumulative median (Q1, Q3) denosumab exposure was 19.1 (9.2, 32.2) months in the breast cancer trial (n = 1019) and 12.0 (5.6, 21.3) months in the prostate cancer trial (n = 942); 295 patients received denosumab for >3 years. No new safety signals were identified during the open-label phase, or among patients who switched from ZA to denosumab. During the blinded treatment phase, exposure-adjusted subject incidences of osteonecrosis of the jaw (ONJ) were 49 (1.9%) and 31 (1.2%) in the denosumab and ZA groups, respectively. In total, 32 (6.9%) and 25 (5.5 %) new cases of ONJ (not adjusted for exposure) were reported for patients continuing and switching to denosumab, respectively. The incidences of hypocalcemia were 4.3 and 3.1%, in patients continuing and switching to denosumab, respectively.

conclusionThese results describe the safety profile of denosumab after long-term exposure, or after switching to denosumab from ZA. No new safety signals were identified. Hypocalcemia rates were similar in the blinded treatment and open-label phases. ONJ rates increased with increasing exposure to antiresorptives, consistent with previous reports.

Indexed as

Breast NeoplasmsProstatic NeoplasmsAdministration, CutaneousAgedAntibodies, Monoclonal, HumanizedBone Density Conservation AgentsBone NeoplasmsDenosumabDiphosphonatesDouble-Blind MethodDrug Administration ScheduleFemaleHumansImidazolesInfusions, IntravenousLong-Term CareAntibodies, Monoclonal, HumanizedBone Density Conservation AgentsDenosumabDiphosphonatesImidazolesZoledronic AcidBone metastasesBreast cancerDenosumabOsteonecrosis of the jawProstate cancerZoledronic acid

Identifiers

PMID26335402
PMCPMC4669370

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.