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

Abstract

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.

Population Modeling Integrating Pharmacokinetics, Pharmacodynamics, Pharmacogenetics, and Clinical Outcome in Patients With Sunitinib‐Treated Cancer

“…For the underlying PK/PD analysis, data were used from two PK studies, which focused on sunitinib treatment in patients with mRCC and patients with mCRC. 23,25 Both studies were designed as prospective, open label, single arm, multicenter, nonrandomized studies and performed in accordance with the Declaration of Helsinki. Patients gave written informed consent to give venous blood for PK/PD analysis and genotyping taken in the course of routine blood draw, and allowed the study sites to document clinical data.…”

“…The C-IV-001 study (EudraCT-No: 2012-001415-23) was a phase IV PK/PD substudy of the noninterventional Euro-TARGET project. 23 Patients with mRCC were recruited in 9 medical centers in Germany and The Netherlands. Sunitinib doses ranged from 37.5-50 mg daily in the 4-week on/2week off scheme.…”

“…Within the EuroTARGET project, PFS was evaluated as the primary endpoint. 23 The C-II-005 study (EudraCT-No: 2008-00151537) was performed to investigate the beneficial effect of sunitinib as add-on to biweekly folinate, fluorouracil, and irinotecan in patients with mCRC and liver metastases. 25 Patients received a daily dose of 37.5-mg sunitinib on a 4-week on/2-week off treatment schedule.…”

“…This is part of the objectives of the European collaborative project Euro-TARGET. 23 Several PK models for sunitinib have previously been published. Here, we used a nonlinear mixed-effects PK model for analyzing data of both patients with mRCC and patients with metastasized colorectal cancer (mCRC) in a pooled dataset.…”

“…Here, we used a nonlinear mixed-effects PK model for analyzing data of both patients with mRCC and patients with metastasized colorectal cancer (mCRC) in a pooled dataset. [23][24][25][26] This model was linked to PD models for sVEGFR-2 and sVEGFR-3, which were previously developed by our group. 27 The purpose of our study was the development of PK models, linking sunitinib plasma concentrations to PD response, and clinical outcome in a model-based time-to-event (TTE) analysis, including the identification of potential genetic predictors.…”