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Translational research

3897 - Development of the Manchester Cancer Research Centre Molecular Tumour Board for matching patients to clinical trials based on tumour and ctDNA genetic profiling.

Date

09 Sep 2017

Session

Translational research

Presenters

Avinash Gupta

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

A. Gupta1, M. Ayub2, C. Miller3, D. Rothwell2, A. Wallace4, A. Jordan5, N. Cook6, F. Thistlethwaite6, L. Carter6, C. O’brien6, S. Aruketty6, E. Dean6, A. Hudson7, K. Frese2, J. Dransfield6, A. Hughes6, R. Marais8, C. Dive2, G. Brady2, M. Krebs6

Author affiliations

  • 1 Experimental Cancer Medicine Team, Christie NHS Trust/University of Manchester, M20 - Manchester/GB
  • 2 Clinical And Experimental Pharmacology Group, Cancer Research UK Manchester Institute, Manchester/GB
  • 3 Cruk Rna Biology Group, Cancer Research UK Manchester Institute, Manchester/GB
  • 4 Genomic Medicine, Manchester Centre for Genomic Medicine, Manchester/GB
  • 5 Drug Discovery Unit, CRUK Manchester Institute, Manchester/GB
  • 6 Experimental Cancer Medicine Team, Christie NHS Trust/University of Manchester, Manchester/GB
  • 7 Department Of Medical Oncology, The Christie NHS Foundation Trust, Manchester/GB
  • 8 Molecular Oncology Group, Cancer Research UK Manchester Institute, Manchester/GB
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Abstract 3897

Background

Advances in Next Generation Sequencing (NGS) are enabling detailed molecular analysis of tumour and circulating tumour DNA (ctDNA). Combined with the expanding development of targeted therapies we are in the era of Precision Medicine. Molecular Tumour Boards (MTB) are needed to interpret genomic data and inform on clinically relevant matched therapies. We describe our experience of setting up a MTB to deliver a world-class genomic driven oncology programme.

Methods

Patients referred to the Experimental Cancer Medicine Team were consented for analysis of ctDNA and tumour under the TARGET (Tumour ChAracterisation to Guide Experimental Targeted Therapy) protocol. ctDNA was subjected to NGS and bioinformatic analysis for alterations in 650 cancer associated genes. Tumour was analysed by NGS for a panel of 24 genes regarded as relevant for treatment of solid tumours. We established a MTB comprising medical oncologists, clinical geneticists, bioinformaticians, scientists and bioethicists to interpret results and advise on clinical relevance and trial options. The aim of Part A of TARGET was to establish workflow and process.

Results

From Apr 2015 to Nov 2016 we recruited 100 patients to Part A. Main tumour types were colorectal (24%), breast (20%) and lung (18%). In 41% of patients a potentially actionable aberration was identified. The main challenges were i) optimisation of a bioinformatic pipeline for ctDNA, ii) linking clinical data with genomic data in a single portal, iii) interpretation of unknown variants and iv) linking results to available clinical trials in UK/Europe.

Conclusions

We have successfully implemented a comprehensive molecular profiling programme. The bioinformatic pipeline for ctDNA has evolved through real-life data collection and comparison with tumour/germline DNA. We are developing a web-based interface for linking clinical and genomic data for visualisation and annotation within the MTB. Variant interpretation software packages are being evaluated for data curation and ability to link with matched clinical trials. Recruitment of 450 patients to Part B of TARGET is underway to match patients with early phase trials in real-time.

Clinical trial identification

CFTSp094

Legal entity responsible for the study

Study sponsor is The Christie NHS Foundation Trust

Funding

The Christie NHS Foundation Trust, Manchester Cancer Research Centre, CRUK Major Centre award

Disclosure

A. Wallace: Speaker services for Astra Zeneca and Merck-Serono F. Thistlethwaite: Advisory boards: BMS, Pfizer. Speakers honoraria: Novartis, BMS. Travel support: BMS, Ipsen. Other (service support): Novartis, Pfizer. E. Dean: Currently employed by AstraZeneca. No stock or advisory roles. A. Hughes: Shareholder in AstraZeneca and remunerated consultancy for AstraZeneca, Roche, Leo Pharmaceuticals, Aptus Clinical, Carrick Therapeutics and PCI Biotech M. Krebs: Consultancy for Roche All other authors have declared no conflicts of interest.

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