European screening platform for EORTC clinical trials in advanced colorectal cancer ‘SPECTAcolor’

Abstract

Background The European Organisation for Research and Treatment of Cancer (EORTC) has established the Screening Platform for Efficient Clinical Trial Access for COLORectal Patients (SPECTAcolor), which provides centralized molecular testing to screen patients for and facilitate enrollment in molecular-based therapeutic trials. Materials and methods Patients with advanced or metastatic colorectal malignancies were recruited in 11 European countries. Patients’ paraffin-embedded material was tested for KRAS, NRAS, BRAF, and PI3K microsatellite instability-high (MSI-H) (not routine at the time of recruitment) and later by a 300-gene next-generation sequencing panel. RNA profiling was carried out in a subset of patients. Results were reported to the centers and patients were followed up for their clinical outcome. Results Recruitment began in September 2013. The molecular screening program was completed at the end of 2015. A total of >1000 patients were prospectively recruited into SPECTAcolor. Molecular and complete clinical/follow-up data are available for 845 metastatic colorectal cancer (CRC) patients. The simple κ coefficient for the agreement between local and central testing for KRAS, NRAS, and BRAF was 0.82-0.95, and the κ for MSI-H was 0.55. The median overall survival was 56.6 months. Patients with BRCA, FGFR, and HER2 alterations had a trend toward shorter survival. Conclusion SPECTAcolor demonstrated that recruitment to an academic screening platform is feasible and that central (quality-assured) testing may remain necessary even for commonly tested markers. SPECTAcolor has generated a clinical and molecular dataset with associated samples for >800 CRC patients for future academic research such as biomarker validation. Linking screening platforms to therapeutic trials and ensuring sustainability remain challenging.