Evidence map›Paper›PMID 37284523›Full record

ArticleTherapeutic advances in medical oncology2023

Adjuvant denosumab in early breast cancer: a systematic review and meta-analysis of randomized controlled clinical trials.

Luca Mastrantoni, Giovanna Garufi, Elena Di Monte, Noemi Maliziola, Mariangela Pasqualoni, Letizia Pontolillo, Sergio Pannunzio, Maria Chiara Cannizzaro, Armando Di Bello, Alessandra Fabi and 4 more

Open access · goldAbstract read
In one paragraph

Article in Therapeutic advances in medical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 12% 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.

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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Luca MastrantoniDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, via della Pineta Sacchetti, 217, Rome 00168, Italy.ORCID https://orcid.org/0000-0003-1853-4927
Giovanna GarufiDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Elena Di MonteDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Noemi MaliziolaDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Mariangela PasqualoniDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Letizia PontolilloDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Sergio PannunzioDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Maria Chiara CannizzaroDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Armando Di BelloDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Alessandra FabiPrecision Medicine Breast Unit, Scientific Directorate, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Antonella PalazzoDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Giampaolo TortoraDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Emilio BriaDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.
Armando OrlandiDepartment of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.ORCID https://orcid.org/0000-0001-5253-4678
Università Cattolica del Sacro Cuore · ITAgostino Gemelli University Polyclinic · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: In early breast cancer (BC) the impact of denosumab on survival outcomes is still unclear. We undertook a systematic review and meta-analysis to assess efficacy and safety of adjuvant denosumab in addition to standard anticancer therapy. Methods: PubMed, CENTRAL, Scopus, Embase, and oncological meetings websites were screened to identify potentially eligible randomized controlled trials (RCTs). Survival outcomes were disease-free survival (DFS), bone-metastasis-free survival (BMFS), and overall survival (OS). Fracture incidence and time to first fracture were bone-health outcomes. Osteonecrosis of the jaw (ONJ), atypical femur fractures (AFF), and other adverse events were also evaluated. Pooled hazard ratios (HRs) and risk ratios (RR) with respective 95% confidence interval (95% CI) were computed using a random-effects model. Exploratory subgroup analyses were performed. Results: Two phase III RCTs were included, the Austrian Breast & Colorectal Cancer Study Group-18 (ABCSG-18) and the D-CARE trials, for a total of 7929 patients. In the ABCSG-18 trial, denosumab was administered every 6 months during endocrine therapy (for a median of seven cycles) while the D-CARE trial used an intensive schedule for a total treatment duration of 5 years. Adjuvant denosumab showed no difference in DFS (HR: 0.932; 95% CI: 0.748-1.162), BMFS (HR: 0.9896; 95% CI: 0.751-1.070), and OS (HR: 0.917; 95% CI: 0.718-1.171) compared to placebo in the overall population. In hormone receptor positive/human epidermal growth factor receptor 2 (HER2) negative BC patients, a DFS (HR: 0.883; 95% CI: 0.782-0.996) and BMFS (HR: 0.832; 95% CI: 0.714-0.970) benefit was observed and BMFS was prolonged in all hormone receptor positive patients (HR: 0.850; 95% CI: 0.735-0.983). Fracture incidence (RR: 0.787; 95% CI: 0.696-0.890) and time to first fracture (HR: 0.760; 95% CI: 0.665-0.869) were also improved. No increase in overall toxicity was seen with denosumab and no differences were observed for ONJ and AFF between the 60-mg every 6-month schedule and placebo. Conclusion: Denosumab addition to anticancer treatment does not improve DFS, BMFS, or OS in the overall population, although a DFS improvement was observed in hormone receptor positive/HER2 negative BC patients and a BMFS improvement in all hormone receptor positive patients. Bone-health outcomes were improved with no added toxicity with the 60-mg schedule. Registration: PROSPERO identifier: CRD42022332787.

Indexed as

adjuvant therapybone-healthdenosumabearly breast cancermeta-analysis

Identifiers

PMID37284523
PMCPMC10240867
OpenAlexW4378717410

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.