The efficacy and safety of zoledronic acid and strontium-89 in treating non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

Background Zoledronic acid (ZA) and strontium-89 have been widely used to treat lung cancer with bone metastases. The authors perform this meta-analysis to better evaluate the clinical outcome of ZA and strontium-89 for non-small cell lung cancer (NSCLC) patients. Methods We carried out standard meta-analysis and network meta-analysis based on a comprehensive data retrieval of EMBASE, PubMed, and Cochrane Library databases (up to March 2019). Random and fixed effects models were used where indicated and between-study heterogeneity was assessed. The primary endpoints were overall survival (OS) and skeletal-related events (SREs). The second endpoints were progression-free survival (PFS) and overall response rate (ORR). Results Seven randomized clinical trials, including 1426 NSCLC patients with seven studies of zoledronic acid and two studies of strontium-89, met the inclusion criteria. Compared with the control group, ZA is associated with a OS benefit (1-year survival rate: RR = 1.76, 95% CI 1.36-2.27; and 24-month survival rate: RR = 2.38, 95% CI 1.35-4.19) and a reduction of SREs (RR = 0.57, 95% CI 0.40-0.84) for the patients with bone metastases. No statistical differences were found in PFS and ORR. Network meta-analysis for the patients with bone metastases showed that ZA + strontium-89 and ZA harbored significantly clinical benefits than strontium-89 and placebo in terms of 1-year survival rate and SREs. Both head-to-head study and network meta-analysis showed that strontium-89 had no statistical impact on OS and SREs compared with placebo. Conclusion Our analysis demonstrates that ZA +strontium-89 can be considered a priority for NSCLC patients with bone metastases, followed by ZA.