Description of the EuroTARGET cohort: A European collaborative project on TArgeted therapy in renal cell cancer-GEnetic- and tumor-related biomarkers for response and toxicity

Urol Oncol. 2017 Aug;35(8):529.e9-529.e16. doi: 10.1016/j.urolonc.2017.03.009. Epub 2017 Apr 3.

Abstract

Objective: For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort.

Methods and materials: EuroTARGET is a European collaborative project designed as an observational study for which patients with mRCC were recruited prospectively in 62 centers. In addition, 462 patients with mRCC from previous studies were included. Detailed clinical information (baseline and follow-up) from all patients was entered in web-based case record forms. Blood was collected for germline DNA and pharmacokinetic/pharmacodynamic analyses and, where available, fresh-frozen tumor material was collected to perform tumor DNA, RNA, kinome, and methylome analyses.

Results: In total, 1,210 patients with mRCC were included. Of these, 920 received a tyrosine kinase inhibitor as first-line targeted treatment (sunitinib [N = 713, 78%], sorafenib [N = 41, 4%], or pazopanib [N = 166, 18%]) and had at least 6 months of outcome assessment (median follow-up 15.3 months [interquartile range: 8.5-30.2 months]). Germline DNA samples were available from 824 of these patients, fresh-frozen tumor material from 142 patients, fresh-frozen normal kidney tissue from 95 patients, and tissue microarrays created from formalin-fixed paraffin-embedded tumor material from 247 patients. Of the 920 patients, germline DNA variant chip data were successfully generated for 811 patients (Illumina HumanOmniExpress BeadChip). For 80 patients, next-generation exome sequencing of germline and tumor DNA was performed, tumor RNA sequencing was performed for 124 patients, kinome activity measured and processed for 121 patients (PamChip), and methylome data (Illumina Infinium HumanMethylation450 BeadChip) were created for 116 RCC tissues (and 23 normal kidney tissues). For 73 out of the 920 patients, all platform data types were generated. In addition, 40 patients were included in a pharmacokinetic/pharmacodynamic phase IV substudy.

Conclusions: Analysis of EuroTARGET cohort data will contribute to personalization of therapy for patients with mRCC. The extensive clinical data and multiplatform EuroTARGET data will be freely available.

Keywords: Biomarker; Genomics; Metastatic renal cell carcinoma; Therapy response; Transcriptomics; Tyrosine kinase inhibitor.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics
  • Cohort Studies
  • Female
  • Humans
  • Indoles / therapeutic use
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / therapeutic use
  • Pyrroles / therapeutic use
  • Sorafenib
  • Sulfonamides / therapeutic use
  • Sunitinib
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Indoles
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • Niacinamide
  • pazopanib
  • Sorafenib
  • Sunitinib