IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma

Br J Cancer. 2015 Mar 31;112(7):1190-8. doi: 10.1038/bjc.2015.64.

Abstract

Background: We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC).

Methods: The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3).

Results: In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients.

Conclusions: Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics*
  • Clinical Trials, Phase III as Topic
  • Female
  • Humans
  • Indazoles
  • Indoles / therapeutic use*
  • Interleukin-8 / genetics*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pyrimidines / therapeutic use*
  • Pyrroles / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sulfonamides / therapeutic use*
  • Sunitinib
  • Survival Analysis
  • Young Adult

Substances

  • Antineoplastic Agents
  • CXCL8 protein, human
  • Indazoles
  • Indoles
  • Interleukin-8
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • pazopanib
  • Sunitinib