Endostar continuous versus intermittent intravenous infusion combined with chemotherapy for advanced NSCLC: a systematic review and meta-analysis including non-randomized studies

Abstract

Background: Both intermittent intravenous (IIV) infusion and continuous intravenous (CIV) infusion of Endostar are widely used for NSCLC in China. We aimed to compare the efficacy and safety of CIV of Endostar versus IIV in combination with first-line chemotherapy for patients with advanced NSCLC. Methods: RCTs, NRCTs and cohort studies which compared CIV of Endostar with IIV in advanced NSCLC patients and reported efficacy or safety outcomes were eligible. Two reviewers independently screened records, extracted data and assessed risk of bias. Pooled risk ratios (RRs) with 95% confidence intervals were calculated using random effects meta-analysis for short-term efficacy and safety outcomes, and hazard ratios (HRs) for survival outcomes. Results: Finally nine studies involving 597 patients were included, containing two RCTs, three NRCTs and four cohort studies. For short-term efficacy, moderate quality of evidence showed that there were no significant differences between CIV of Endostar and IIV in objective response rate (ORR; RR 1.34, 95% CI 0.91–1.98, P = 0.14) and disease control rate (DCR; RR 1.11, 95% CI 0.94–1.30, P = 0.21). Very low quality of evidence indicated that CIV of Endostar significantly improved both overall survival (OS; HR 0.69, 95% CI 0.48–0.99, P = 0.046) and progression-free survival (PFS; HR 0.71, 95% CI 0.55–0.93, P = 0.01) compared with IIV. As for safety outcomes, moderate quality of evidence found that CIV of Endostar significantly reduced the risk of myelosuppression (RR 0.55, 95% CI 0.32–0.96, P = 0.03) and cardiovascular toxicity (RR 0.21, 95% CI 0.06–0.78, P = 0.02) compared with IIV. Conclusions: In advanced NSCLC, compared with IIV, CIV of Endostar had similar short-term efficacy, and substantially lower risk of myelosuppression and cardiovascular toxicity. Although very low quality of evidence supported the survival benefit of CIV compared with IIV, large RCTs with long-term follow-up are needed to demonstrate survival benefits. Caution should be given for off-label use of CIV of Endostar.