Efficacy and safety of aflibercept plus chemotherapy in metastatic colorectal cancer: A systematic review and PRISMA-Compliant single-arm Meta-Analysis of noncomparative clinical studies and randomized controlled trials

J Clin Pharm Ther. 2022 Jun;47(6):798-808. doi: 10.1111/jcpt.13610. Epub 2022 Mar 1.

Abstract

What is known and objective: Aflibercept, a recombinant protein designed to suppress the vascular endothelial growth factor (VEGF) signalling pathway, has been used in patients with metastatic colorectal cancer (mCRC). We conducted the first meta-analysis to systematically review the efficacy and safety of aflibercept in mCRC.

Methods: PubMed Central/Medline, Embase and cochrane library were systematically searched for randomized controlled trials and single-arm clinical trials on aflibercept plus chemotherapy for the treatment of mCRC through 9 September 2021.

Results: Ten studies comprising 2049 patients met the inclusion criteria. The pooled estimate rates were 16.0% for 12mPFS, 64.4% for 12mOS, 32.5% for ORR, 83.5% for DCR, while the rates of III/IV AEs rate were 80.2% respectively. The pooled estimate rates were 16.8% for III/IV diarrhoea, 22.3% for III/IV hypertension, 29.5% for III/IV neutropenia, 7.3% for III/IV proteinuria and 8.6% for III/IV oral mucositis.

Conclusions: Analysis of data from randomized controlled trials(RCT) and single-arm clinical trials confirmed the good efficacy of aflibercept plus chemotherapy in mCRC, while the safety of the treatment is concerning.

Keywords: aflibercept; chemotherapy; colorectal cancer; meta-analysis; systematic review; targeted therapy.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Colonic Neoplasms* / drug therapy
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Fluorouracil / therapeutic use
  • Humans
  • Randomized Controlled Trials as Topic
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use
  • Recombinant Fusion Proteins / adverse effects
  • Rectal Neoplasms* / drug therapy
  • Vascular Endothelial Growth Factor A

Substances

  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor
  • Fluorouracil