Molecular characteristics of patients' (pts) tumours can determine suitability for targeted drugs, but many variants are only seen in a small percentage of pts. Targeted next generation sequencing (NGS) can be used to screen tumours for multiple variants and therefore facilitate precision medicine, but details are lacking on the practicality of this approach.
The FOrMAT study (ClinicalTrials.gov identifier NCT02112357) is a single-centre study in pts with advanced GI cancer. The study aimed to investigate the feasibility of delivering NGS results (to accredited standards) in a clinically meaningful timeframe and how this could be adopted into routine clinical practice in the United Kingdom's National Health Service (NHS). Targeted capture sequencing (mainly using archival formalin fixed paraffin embedded samples from referring hospitals) was performed to detect mutations, copy number variations and translocations in 46 genes which had prognostic/predictive significance or were targets in current/future clinical trials.
Between February 2014 – November 2015, 222 pts were recruited and samples obtained for 215 pts. Of these 215 pts, NGS results for ≥ 16 of the 46 genes were obtained for 125 pts (58%) and for ≥ 1 genes in 136 pts (63%). Potentially actionable variants were detected in 90 pts. NGS success rates (results for ≥ 16 genes) improved during the study (1st pt cohort vs last pt cohort: 52% vs 65%). The proportion of successfully sequenced samples was influenced by sample characteristics, e.g. tumour cellularity (high vs low: 78% vs 13%, p =
NGS was not successfully performed in 44% of patients recruited to this study because of unavailable/inadequate tissue samples. In order for NGS to become feasible within a routine NHS setting, pathways for tissue collection and processing need to be optimised so that results can be obtained in a clinically useful timeframe.
Clinical trial identification
ClinicalTrials.gov NCT02112357; Protocol V4.0, dated 10.04.15
Legal entity responsible for the study
The Royal Marsden NHS Foundation Trust
National Institute for Health Research Royal Marsden/Institute of Cancer Research Biomedical Research Centre The Moodie Report Foundation The Clive and Ann Smith Fellowship
All authors have declared no conflicts of interest.