The impact of angiogenesis inhibitors on survival of patients with small cell lung cancer

Cancer Med. 2019 Oct;8(13):5930-5938. doi: 10.1002/cam4.2462. Epub 2019 Aug 21.

Abstract

Background: Small cell lung cancer (SCLC) is a highly invasive and lethal neuroendocrine tumor. Antiangiogenic drugs have been reported in the treatment of SCLC. We aimed to provide a comprehensive evaluation of the impact of angiogenic inhibitors on SCLC survival using network meta-analysis.

Methods: The impact of five angiogenesis inhibitors, that is, vandetanib (Van), bevacizumab (Bev), Rh-endostatin (End), sunitinib (Sun), and thalidomide (Tha), on progression-free survival (PFS) and overall survival (OS) was evaluated by conducting a network meta-analysis. RNA sequencing data were downloaded from publicly available databases.

Results: Nine phase II and III randomized controlled trials (RCTs), that involved 1599 participants, that investigated angiogenesis inhibitors in the treatment of SCLC were included in this meta-analysis. Sun and Bev achieved better PFS than Tha (Bev VS. Tha, HR = 0.88, 95% CI: 0.79-0.98, Sun VS. Tha, HR = 0.80, 95% CI: 0.65-1.00). Moreover, Sun and Bev were superior to placebo in terms of PFS (Bev VS. Placebo, HR = 0.89, 95%CI: 0.81-0.97, Sun VS. Placebo, HR = 0.81, 95% CI: 0.66-1.00). Based on this study, we found no significant difference of OS of SCLC. The angiogenesis pathway and expression of target genes were globally deactivated in SCLC tissue.

Conclusion: Results of this network meta-analysis indicate that the PFS outcome of SCLC with Sun or Bev drugs is superior to that of Tha. The improved therapeutic impact of angiogenesis inhibitors on SCLC needs more evidence, such as long-term observation in clinical trials, to be validated.

Keywords: angiogenesis inhibitors; network meta-analysis; randomized controlled trial; small cell lung cancer; target drugs.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • RNA-Seq
  • Randomized Controlled Trials as Topic
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / genetics

Substances

  • Angiogenesis Inhibitors