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Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer?

Oncotarget. 2015 Jul 20;6(20):18206-23. doi: 10.18632/oncotarget.4524.

Abstract

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) might be new therapeutic strategies for advanced non-small cell lung cancer (NSCLC). Here a total of 12,520 patients from 23 randomized controlled trials (RCTs) were enrolled to evaluate the efficacy and safety of VEGFR-TKIs quantitatively in advanced NSCLC. Compared with non-VEGFR-TKIs, VEGFR-TKIs regimen significantly improved progression-free survival (PFS) [hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.805-0.874, P < 0.001], objective response rates (ORR) [relative risk (RR): 1.374, 95%CI: 1.193-1.583, P < 0.001] and disease control rates (DCR) (RR: 1.113, 95%CI: 1.027-1.206, P =0.009), but not overall survival (OS) (HR: 0.960, 95%CI: 0.921-1.002, P =0.060) for NSCLC patients. The RR of all-grade neutropenia, thrombocytopenia, hypertension, hemorrhage, fatigue, anorexia, stomatitis, diarrhea, rash, hand-foot skin reaction (HFSR) were increased in patients received VEGFR-TKIs. As for high-grade (≥3) adverse events (AEs), VEGFR-TKIs were associated with higher RR of neutropenia, thrombocytopenia, hypertension, fatigue, stomatitis, diarrhea, rash and HFSR. This study demonstrates VEGFR-TKIs improve PFS, ORR and DCR, but not OS in advanced NSCLC patients. VEGFR-TKIs induce more frequent and serious AEs compared with control therapies.

Keywords: TKIs; VEGFR; angiogenesis inhibitors; lung cancer; meta analysis.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chi-Square Distribution
  • Disease Progression
  • Disease-Free Survival
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Odds Ratio
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Risk Factors
  • Signal Transduction / drug effects
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, Vascular Endothelial Growth Factor