Pharmacogenomic analyses of sunitinib in patients with pancreatic neuroendocrine tumors

Future Oncol. 2019 Jun;15(17):1997-2007. doi: 10.2217/fon-2018-0934. Epub 2019 May 14.

Abstract

Aim: Evaluate associations between clinical outcomes and SNPs in patients with well-differentiated pancreatic neuroendocrine tumors receiving sunitinib. Patients & methods: Kaplan-Meier and Cox proportional hazards models were used to analyze the association between SNPs and survival outcomes using data from a sunitinib Phase IV (genotyped, n = 56) study. Fisher's exact test was used to analyze objective response rate and genotype associations. Results: After multiplicity adjustment, progression-free and overall survivals were not significantly correlated with SNPs; however, a higher objective response rate was significantly associated with IL1B rs16944 G/A versus G/G (46.4 vs 4.5%; p = 0.001). Conclusion: IL1B SNPs may predict treatment response in patients with pancreatic neuroendocrine tumors. VEGF pathway SNPs are potentially associated with survival outcomes.

Keywords: VEGF; biomarkers; efficacy; pancreatic neuroendocrine tumor; sunitinib.

Publication types

  • Clinical Trial, Phase IV

MeSH terms

  • Aged
  • Female
  • Humans
  • Interleukin-1beta / genetics*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / mortality
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality
  • Pharmacogenomic Testing
  • Polymorphism, Single Nucleotide
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Sunitinib / administration & dosage*
  • Sunitinib / adverse effects

Substances

  • IL1B protein, human
  • Interleukin-1beta
  • Protein Kinase Inhibitors
  • Sunitinib