Endostar continuous versus intermittent intravenous infusion combined with chemotherapy for advanced NSCLC: a systematic

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RESEARCH ARTICLE

Open Access

Endostar continuous versus intermittent intravenous infusion combined with chemotherapy for advanced NSCLC: a systematic review and meta-analysis including non-randomized studies Bo Wang1†, Lu Xu2†, Qihuan Li1, Sailimai Man1,2, Cheng Jin3, Lian Liu4, Siyan Zhan2,5* and Yi Ning1*

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. Keywords: Recombinant human endostatin, Endostar, Non-small cell lung cancer, Systematic review, Meta-analysis, Non-randomized studies * Correspondence: [email protected]; [email protected] † Bo Wang and Lu Xu contributed equally to this work. 2 Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China 1 Department of Epidemiology, Meinian Institute of Health, Beijing, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduc