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

被引：6

作者：

Mastrantoni, Luca ^{[1
]}

Garufi, Giovanna ^{[2
,3
]}

Di Monte, Elena ^{[4
]}

Maliziola, Noemi ^{[4
]}

Pasqualoni, Mariangela ^{[4
]}

Pontolillo, Letizia ^{[4
]}

Pannunzio, Sergio ^{[4
]}

Cannizzaro, Maria Chiara ^{[4
]}

Di Bello, Armando ^{[4
]}

Fabi, Alessandra ^{[5
]}

Palazzo, Antonella ^{[2
,3
]}

Tortora, Giampaolo ^{[2
,3
]}

Bria, Emilio ^{[2
,3
]}

Orlandi, Armando ^{[2
,3
]}

机构：

[1] Univ Cattolica Sacro Cuore, Dept Med Oncol, Via Pineta Sacchetti 217, I-00168 Rome, Italy

[2] Univ Cattolica Sacro Cuore, Dept Med Oncol, Rome, Italy

[3] IRCCS, Fdn Policlin Univ Agostino Gemelli, Comprehens Canc Ctr, Rome, Italy

[4] Univ Cattolica Sacro Cuore, Dept Med Oncol, Rome, Italy

[5] Fdn Policlin Univ Agostino Gemelli IRCCS, Dept Women Children & Publ Hlth Sci, Precis Med Breast Unit, Sci Directorate, Rome, Italy

来源：

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY | 2023年 / 15卷

关键词：

adjuvant therapy; bone-health; denosumab; early breast cancer; meta-analysis; REAL-WORLD ADHERENCE; ZOLEDRONIC ACID; POSTMENOPAUSAL OSTEOPOROSIS; RANKL INHIBITION; BONE-METASTASIS; D-CARE; THERAPY; BISPHOSPHONATES; WOMEN; MULTICENTER;

D O I：

10.1177/17588359231173180

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：20

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