Cancer Research UK Stratified Medicine Programme J. Peach, F.M. Hemsley, L. K. Jones, M.C.M. Jones, E. Smith, A. Tuff, P. W. M. Johnson Cancer R C Research UK L d h UK, London, UK email@example.com UK. t tifi d di i @ k VISION Funding partnership Figure 1. Phase One ModelGovernment, charity and commercial organisations have formed a partnership to help the NationalHealth Service (NHS) adopt new targeted therapies, as well as making the UK a better place for research The programme relies on cross organisational working. Core funding is provided by CR-UK,into more personalised cancer treatment. AstraZeneca and Pfizer.Our vision is to establish a national molecular diagnostics service delivering high quality, cost effective The TSB are investing £5.6 million in support of the programme. They aretests for patients, with routine consent for the collection, storage and research use of genetic, treatment TSB CRUK, 50% funding industry led collaborations to develop a panel of genetic assays AZ, and outcomes data. costing £300 or less, or an informatics system. The collaborations will grantees £5.6m £5 6m Pfizer match f di provided b th TSB t h funding id d by the TSB. £5.5m Introduction and specific objectives of Phase One The programme is also coordinated with the Department of Health, the TSB National Institute of Health and Clinical Excellence, the Human Genomic £5.6mAdvances in our understanding of the molecular genetics of cancer enable clinicians to stratify patients Strategy Group and the Medical Research Council, who are represented onby the molecular characteristics of their tumours, thereby ensuring patients receive targeted treatments our programme boards.with fewer side effects and better outcomes. This approach, which we have called “stratified medicine”,is in its infancy in the NHS but shows great promise. Cancer Research UK (CR-UK) has built a The Department of Health recently published “Improving outcomes - a strategy for cancer” which statespartnership with pharmaceutical companies and the government to improve molecular diagnostic that the ‘DH will develop a commissioning and funding structure to enable the efficient delivery of hightesting for cancer patients in the UK, while capturing genetic data so that we can compare it to patient (Laboratories) quality molecular diagnostic testing through centres of excellence’.outcomes to inform future research.1. Service delivery - improve molecular profiling Anticipated outcomes of Phase One To demonstrate molecular characterisation of tumours as a standardised, cost-effective, routine 1. Demonstrate large scale, quality assured molecular diagnostic testing for NHS patients across the practice in the treatment of cancer patients in the NHS. This will be scalable, and ready to integrate major solid tumour types including: the new technologies, tests and treatments that we believe are imminent. • A consent process that allows patient’s nucleic acid to be tested prospectively and retrospectively2. Research - capture clinical and genetic research data for genetic markers and the data generated to be used for research purposes; • Up to 9,000 samples across six major solid tumours analysed for c.20 markers; To consent cancer patients for research and capture routine NHS clinical data to form cohort • Genetic information returned in a clinically relevant timeframe. datasets of mutations, treatments and outcomes. 2. Develop an informatics system that: • Can capture high quality, standardised molecular diagnostic information about malignant tumours; Phase One (2011-2013): model of the processes required to • Securely stores data; routinely test molecular characteristics of tumours from • Provides a flexible web accessible interface that permits search and retrieval of anonymised diagnostic, treatment and outcome data for those with appropriate access rights within a defined cancer patients and to securely store and retrieve molecular timeframe; and clinical data for research. • Has the capability to link to other data sets.• Phase One will involve seven existing Experimental Cancer Medicine Centres (ECMCs) (Figure 1) g p ( )( g ) Figure 2. Genes/mutations targeted 3. Deliver a standardised and validated broad panel of genetic assays testing common and relevant consenting up to 9,000 patients with six tumour types; breast, colorectal, lung, prostate, ovary and mutations for £300 or less. metastatic melanoma. Tumour Type Gene Mutation• Surplus material from biopsies or resections will be sent to one of three centralised, externally quality assured technology hubs (CPA accredited laboratories) where nucleic acid will be extracted and Colorectal KRAS Codons, 12, 13, 61, 146 Long term strategy tested for a prioritised set of genes and mutations, including existing biomarkers linked to treatment BRAF Exon 15 / codons 599, 600, 601 (Figure 2). NRAS Codons 12, 13, 61 Phase 2 Phase 3• Results of molecular analysis will be made available to clinical teams involved in patient care as well PIK3CA Exons 9 and 20 Medium-term strategy Long-term strategy as being stored for potential, appropriate future research use. Routine clinical information will also g p , pp p TP53 Exons 4‐9 Breast PIK3CA Exons 9 and 20 • K aim i t i t Key i is to integrate lessons l t l learned f d from • National consolidated molecular be collected for five years following diagnosis. Phase One into broader practice in NHS. diagnostics service delivering quality TP53 Exons 4‐9• The programme will deliver a multi-site informatics system for the capture, storage, access and Other possible options inlcude: assured, continuously improving and cost PTEN Exons 2‐10 effective tests for NHS patients. analysis of routinely collected clinical and genetic data in Phase One. The solution will seek to utilise PTEN LOH • Extend scope, e.g. adopt new technologies, existing ECMCs’ data capture capability (with appropriate information governance) and enhance • Research consent is routine practice for Prostate PTEN Exons 2‐10 additional cancer types, broader utility and these through the use of centrally provided applications to ensure interoperability based on known NHS genetic diagnostics. linkage of datasets. information standards. Characteristics of the system will be: PTEN LOH • Focus on research aspects, e.g. profile of • The UK becomes an better place for TMPRSS‐ERG FISH retrieval and integration of diverse NHS datasets concerning cancer patients e.g. national patients recruited, capture non-routine follow- targeted therapies research Lung EGFR Exons 18 – 21 minimum datasets, molecular data and patient records; p up data or deeper analysis on few p p p y patients. maintenance of a secure database where the individual’s right to privacy is demonstrably KRAS Codons 12, 13, 61 and 146 d d EML4‐ALK FISH • Support service deliver improvement, e.g. protected; through government lobbying or local allocation of controlled access to validated members of the research community; BRAF Exon 15 / codon 599, 600, 601 improvement schemes. scalability – any solution will need to be scalable to ultimately incorporate millions of patient Ovary TP53 Exons 4‐9 records, including varied clinical data with the expected massive scale of stratification data PTEN Exons 2‐10 (molecular or imaging) and varieties of formats (images, defined datasets, free text). PTEN LOH Expected long term benefits• The programme will work in partnership with the Technology Strategy Board* (TSB) which is PIK3CA Exons 9 and 20 1. Clinical benefit for patients through higher quality delivery of molecular diagnostics. investing £50 million in stratified medicine in the UK. The TSB is funding industry led collaborations Melanoma BRAF Exons 15 / codons 599, 600, 601 through open competitions to develop a standardised and validated panel of genetic assays that 2. A system in place for clinicians to make treatment decisions based on molecular diagnostic KIT Exons 11 13 and 17 11, 13 and 17 costs £300 or less for delivery within the NHS and an informatics system that can securely capture information as more targeted treatments becomes available. genetic and clinical data on a national level and allow it to be retrieved by clinicians and researchers. NRAS Codons 12, 13, 61 3. Cost savings for the NHS from consolidated and efficient provision of genetic tests, better targeting of PIK3CA Exons 9 and 20 treatment and the avoidance of treatment of side effects of treatment. Disease types, genes and specific mutations are to be tested in Phase One using a 4. National database with cohort datasets of linked genetic and clinical datasets. *The Technology Strategy Board is an executive non-departmental public body, standardised and validated panel of genetic tests. This list will evolve based on increased knowledge of significant pathways and understanding of the link between germline mutations 5. Generation and validation of research hypotheses of new biomarkers. established by the Government in 2007 to stimulate economic growth and sponsored by the Department for Business, Innovation and Skills . and drug response. BRCA is excluded for cost reasons. 6. The UK becomes a more attractive place for investment and innovation in stratified medicine.