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Multi-Targeted Antiangiogenic Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analyses of 20 Randomized Controlled Trials and Subgroup Analyses

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  • Wenhua Liang
  • Xuan Wu
  • Shaodong Hong
  • Yaxiong Zhang
  • Shiyang Kang
  • Wenfeng Fang
  • Tao Qin
  • Yan Huang
  • Hongyun Zhao
  • Li Zhang

Abstract

Background: Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis. Methods: Electronic databases were searched for eligible studies. We defined the experimental arm as MATKI-containing group and the control arm as MATKI-free group. The extracted data on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were pooled. Subgroup and sensitivity analyses were conducted. Results: Twenty phase II/III RCTs that involved a total of 10834 participants were included. Overall, MATKI-containing group was associated with significant superior ORR (OR 1.29, 95% CI 1.08 to 1.55, P = 0.006) and prolonged PFS (HR 0.83, 0.78 to 0.90, P = 0.005) compared to the MATKI-free group. However, no significant improvements in DCR (OR 1.08, 1.00 to 1.17, P = 0.054) or OS (HR 0.97, 0.93 to 1.01, P = 0.106) were observed. Subgroup analyses showed that the benefits were predominantly presented in pooled results of studies enrolling previously-treated patients, studies not limiting to enroll non-squamous NSCLC, and studies using MATKIs in combination with the control regimens as experimental therapies. Conclusions: This up-to-date meta-analysis showed that MATKIs did increase ORR and prolong PFS, with no significant improvement in DCR and OS. The advantages of MATKIs were most prominent in patients who received a MATKI in combination with standard treatments and in patients who had previously experienced chemotherapy. We suggest further discussion as to the inclusion criteria of future studies on MATKIs regarding histology.

Suggested Citation

  • Wenhua Liang & Xuan Wu & Shaodong Hong & Yaxiong Zhang & Shiyang Kang & Wenfeng Fang & Tao Qin & Yan Huang & Hongyun Zhao & Li Zhang, 2014. "Multi-Targeted Antiangiogenic Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analyses of 20 Randomized Controlled Trials and Subgroup Analyses," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-7, October.
    • Handle: RePEc:plo:pone00:0109757
    DOI: 10.1371/journal.pone.0109757
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    1. Peter Carmeliet & Rakesh K. Jain, 2000. "Angiogenesis in cancer and other diseases," Nature, Nature, vol. 407(6801), pages 249-257, September.
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