■在早期乳腺癌(BC)中,denosumab对生存结果的影响尚不清楚。我们进行了系统评价和荟萃分析,以评估除标准抗癌治疗外,辅助denosumab的疗效和安全性。
■PubMed,中部,Scopus,Embase,我们对肿瘤学会议网站进行了筛选,以确定可能符合条件的随机对照试验(RCT).生存结果为无病生存(DFS),无骨转移生存率(BMFS),总生存率(OS)。骨折发生率和首次骨折时间是骨健康结果。颌骨坏死(ONJ),不典型股骨骨折(AFF),和其他不良事件也进行了评估.使用随机效应模型计算具有相应95%置信区间(95%CI)的集合风险比(HR)和风险比(RR)。进行探索性亚组分析。
■包括两个III期随机对照试验,奥地利乳腺癌和结直肠癌研究组-18(ABCSG-18)和D-CARE试验,共7929名患者。在ABCSG-18试验中,在内分泌治疗期间,denosumab每6个月给药一次(中位周期为7个周期),而D-CARE试验采用强化治疗方案,总治疗时间为5年.辅助denosumab在DFS上没有差异(HR:0.932;95%CI:0.748-1.162),BMFS(HR:0.9896;95%CI:0.751-1.070),和OS(HR:0.917;95%CI:0.718-1.171)与安慰剂相比在整个人群中。在激素受体阳性/人表皮生长因子受体2(HER2)阴性的BC患者中,在所有激素受体阳性患者中,观察到DFS(HR:0.883;95%CI:0.782-0.996)和BMFS(HR:0.832;95%CI:0.714-0.970)获益,BMFS延长(HR:0.850;95%CI:0.735-0.983).骨折发生率(RR:0.787;95%CI:0.696-0.890)和首次骨折时间(HR:0.760;95%CI:0.665-0.869)也得到改善。denosumab的总毒性没有增加,并且在每6个月的60-mg时间表和安慰剂之间,ONJ和AFF没有观察到差异。
■Denosumab加入抗癌治疗并不能改善DFS,BMFS,或总体人口中的操作系统,尽管在激素受体阳性/HER2阴性BC患者中观察到DFS改善,在所有激素受体阳性患者中观察到BMFS改善.60mg方案的骨健康结果得到改善,没有增加毒性。
■PROSPERO标识符:CRD42022332787。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: PROSPERO identifier: CRD42022332787.