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. 2018 Sep 21:10:3809-3823.
doi: 10.2147/CMAR.S176811. eCollection 2018.

Efficacy and safety of de-escalation bone- modifying agents for cancer patients with bone metastases: a systematic review and meta-analysis

Cun Liu  1 , Lu Wang  1 , Lijuan Liu  2 , Jing Zhuang  2 , Shifeng Tang  2 , Tiansong Zhang  3 , Chao Zhou  2 , Fubin Feng  2 , Ruijuan Liu  2 , Jinmei Zhang  4 , Tingting Zhang  1 , Chundi Gao  5 , Huayao Li  5 , Jia Li  6 , Changgang Sun  2   7
Affiliations

Efficacy and safety of de-escalation bone- modifying agents for cancer patients with bone metastases: a systematic review and meta-analysis

Cun Liu et al. Cancer Manag Res. .

Abstract

Background: Compared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy.

Methods: A systematic search of PubMed, EMBASE, and the Cochrane Register of Controlled Trials until November 22, 2017, was performed. Randomized controlled trials (RCTs) were included to assess skeletal-related event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12-weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses.

Results: A total of eight citations were eligible comprising 2,878 patients: zoledronate (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87-1.12; P=0.82) for SRE rates between de-escalated and standard arms was produced when seven low risk of bias trials (695 patients) were pooled, and results without statistical significance also appeared in the analysis of adverse events and bone turnover biomarkers. Due to the limited sample size and methodological differences, the data for skeletal morbidity rates (SMRs), time to first SRE, serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but systematic review still obtained similar indistinguishableness.

Conclusion: In this meta-analysis of randomized clinical trials, the results "appeared" to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies.

Keywords: bone metastasis; bone-modifying agents; cancer; de-escalated treatment; meta-analysis.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flow chart of article screening and selection process.
Figure 2
Figure 2
Risk of bias assessment. Note: Green represents low risk of bias; red represents high risk of bias; and yellow represents unclear risk of bias.
Figure 3
Figure 3
Meta-analysis results for skeletal-related events.
Figure 4
Figure 4
Meta-analysis results for bone radiotherapy.
Figure 5
Figure 5
Meta-analysis results for adverse events.
Figure 6
Figure 6
Meta-analysis results for serious adverse events.
Figure 7
Figure 7
Meta-analysis results for bone pain.
Figure 8
Figure 8
Meta-analysis results for renal adverse events.
Figure 9
Figure 9
Meta-analysis results for osteonecrosis of the jaw.
Figure 10
Figure 10
Meta-analysis results for reduction of urine N-telopeptide.
See this image and copyright information in PMC

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