638P - Investigating the feasibility of precision medicine in gastrointestinal cancers

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Gastrointestinal Cancers
Presenter Sing Yu Moorcraft
Citation Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371
Authors S.Y. Moorcraft1, D. Gonzalez De Castro2, D. Cunningham1, B. Walker2, T. Jones2, C. Peckitt1, S. Hulkki Wilson2, A. Wotherspoon3, L.S. Teixeira Mendes3, R. Begum1, Z. Eltahir3, L. Yuan2, A. Gillbanks1, C. Baratelli1, N. Valeri4, M. Gerlinger5, C. Braconi6, I. Chau1, D. Watkins1, N. Starling1
  • 1Gi & Lymphoma Unit, The Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 2Molecular Diagnostics, The Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 3Pathology, The Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 4Laboratory Of Gastrointestinal Cancer Biology And Genomics, Division Of Molecular Pathology, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5NG - Sutton/GB
  • 5Centre For Cancer And Evolution, Institute of Cancer Research ICR, SW7 3RP - London/GB
  • 6Signal Transduction And Molecular Pharmacology, The Institute of Cancer Research ICR, SM2 5NG - Sutton/GB

Abstract

Background

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.

Methods

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.

Results

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 = 

Conclusions

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

Funding

National Institute for Health Research Royal Marsden/Institute of Cancer Research Biomedical Research Centre The Moodie Report Foundation The Clive and Ann Smith Fellowship

Disclosure

All authors have declared no conflicts of interest.