Stratified Medicine Programme Research Articles

Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohorts

Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year. Clusters of MTX 'response' were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65-0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA. Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and the National Institute for Health Research.

The relationship between disease activity and UDCA response criteria in primary biliary cholangitis: A cohort study.

SummaryBackgroundUncertainty exists about how best to identify primary biliary cholangitis (PBC) patients who would benefit from second-line therapy. Existing, purely clinical, ursodeoxycholic acid (UDCA) response criteria accept degrees of liver biochemistry abnormality in responding patients, emerging data, however, suggest that any degree of ongoing abnormality may, in fact, be associated with an increased risk of adverse outcomes. This cohort study explores the link between response status, the biology of high-risk disease and its implications for clinical practice.MethodsProteomics, exploring 19 markers previously identified as remaining elevated in PBC following UDCA therapy, were performed on 400 serum samples, from participants previously recruited to the UK-PBC Nested Cohort between 2014 and 2019. All participants had an established diagnosis of PBC and were taking therapeutic doses of UDCA for greater than 12 months. UDCA response status was assessed using Paris 1, Paris 2 and the POISE criteria, with additional analyses using normal liver blood tests stratified by bilirubin level. Statistical analysis using parametric t tests and 1-way ANOVA.FindingsDisease markers were statistically significantly higher in UDCA non-responders than in responders for all the UDCA response criteria, suggesting a meaningful link between biochemical disease status and disease mechanism. For each of the criteria, however, marker levels were also statistically significantly higher in responders with ongoing liver function test abnormality compared to those who had normalised their liver biochemistry. IL-4RA, IL-18-R1, CXCL11, 9 and 10, CD163 and ACE2 were consistently elevated across all responder groups with ongoing LFT abnormality. No statistically significant differences occurred between markers in normal LFT groups stratified by bilirubin level.InterpretationThis study provides evidence that any ongoing elevation in alkaline phosphatase levels in PBC after UDCA therapy is associated with some degree of ongoing disease activity. There was no difference in activity between patients with normal LFT when stratified by bilirubin. These findings suggest that if our goal is to completely control disease activity in PBC, then normalisation of alkaline phosphatase and bilirubin should be the treatment target. This would also simplify messaging around goals of therapy in PBC, benefiting both patients and clinicians.FundingFunding by the UK Medical Research Council (Stratified Medicine Programme) and an independent research grant by Pfizer. The study funders played no role in the study design, data collection, data analyses, data interpretation or manuscript writing.

The Wales Cancer Bank (WCB)

The Wales Cancer Bank (WCB) was established in 2004 and consents patients in Wales, UK with a known or suspected cancer diagnosis to donate biosamples for future research. The resource is open access to all researchers working in cancer research, regardless of geographic location or employment sector. To December 2017, just over 13,500 patients have donated samples across a variety of tumour types. Tumour and adjacent normal tissue and blood samples are routinely collected, stored and processed to standardised protocols. Bespoke collections for unique samples such as urine or ascites are also available. Pathology data, clinical data including treatment and outcome data and selected molecular data is also available. Funding statement: The WCB is currently funded as part of the Wales Cancer Research Centre by Health and Care Research Wales. Funding is also received from Velindre Charitable funds and Cancer Research UK’s Stratified Medicine Programme. Previous funding has also been received from Cancer Research Wales.

Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme

IntroductionPhase I of the Cancer Research UK Stratified Medicine Programme (SMP1) was designed to roll out molecular pathology testing nationwide at the point of cancer diagnosis, as well as facilitate an infrastructure where surplus cancer tissue could be used for research. It offered a non-trial setting to examine common UK cancer genetics in a real-world context.MethodsA total of 26 sites in England, Wales and Scotland, recruited samples from 7814 patients for genetic examination between 2011 and 2013. Tumour types involved were breast, colorectal, lung, prostate, ovarian cancer and malignant melanoma. Centralised molecular testing of surplus material from resections or biopsies of primary/metastatic tissue was performed, with samples examined for 3–5 genetic alterations deemed to be of key interest in site-specific cancers by the National Cancer Research Institute Clinical Study groups.Results10 754 patients (98% of those approached) consented to participate, from which 7814 tumour samples were genetically analysed. In total, 53% had at least one genetic aberration detected. From 1885 patients with lung cancer, KRAS mutation was noted to be highly prevalent in adenocarcinoma (37%). In breast cancer (1873 patients), there was a striking contrast in TP53 mutation incidence between patients with ductal cancer (27.3%) and lobular cancer (3.4%). Vast inter-tumour heterogeneity of colorectal cancer (1550 patients) was observed, including myriad double and triple combinations of genetic aberrations. Significant losses of important clinical information included smoking status in lung cancer and loss of distinction between low-grade and high-grade serous ovarian cancers.ConclusionNationwide molecular pathology testing in a non-trial setting is feasible. The experience with SMP1 has been used to inform ongoing CRUK flagship programmes such as the CRUK National Lung MATRIX trial and TRACERx.

13 - KRAS Subtypes in non-small cell lung cancer (NSCLC) within Phase I of the Cancer Research UK Stratified Medicine Programme (SMP1)

13 - KRAS Subtypes in non-small cell lung cancer (NSCLC) within Phase I of the Cancer Research UK Stratified Medicine Programme (SMP1)

188 - Getting patients with non-small cell lung cancer on personalised treatment; the experience of Stratified Medicine Programme 2 (SMP2)/National Lung Matrix Trial (NLMT) in North East England

188 - Getting patients with non-small cell lung cancer on personalised treatment; the experience of Stratified Medicine Programme 2 (SMP2)/National Lung Matrix Trial (NLMT) in North East England

Use of NGS for stratification of patients with advanced NSCLC within the NHS using FFPE-extracted DNA from diagnostic biopsies

Background: The Cancer Research UK Stratified Medicine Programme 2 (SMP2) screens NSCLC cancer patients by NGS for clinically-actionable gene aberrations that are likely drug targets. Eligible patients can be recruited to a targeted therapy or ‘Non Actionable (immunotherapy) arm of the National Lung Matrix Trial (NLMT). SMP2 aims to establish genomic screening at a national level within existing NHS pathways and ensure equity of access to targeted therapies to eligible patients in the UK. Methods: The CRUK SMP2 pre-screening programme recruits patients with late stage NSCLC and utilises DNA from excess diagnostic biopsy tissue. Regions of interest are enriched using a custom 28-gene Illumina Nextera Rapid Capture panel before sequencing on MiSeq using V3 chemistry. Validation of the assay involved cell lines, blood and FFPE samples with known aberrations. This comprehensive validation evaluated a number of different factors, including mean target coverage, detection limits, concordance, tumour content cut-off, number of reads required for variant calling, and number of base pairs on either side of the region of interest to be analysed. This validation confirmed that the panel and analytics are able to identify SNV (5% VAF threshold), indels, translocations, amplifications (>5 copies) and deletions (<0.5 fold). The panel confirms wildtype for genes where no aberration is present. CNVs and SVs have been validated against FISH. The analytical pipeline was developed in-house at West Midlands Regional Genetics Service to accommodate a busy diagnostic service, and includes a reporting algorithm for determining confidence in calling wildtype, based on tumour content of the sample, and read depth and coverage achieved. Results: Greater than 3000 patients have been consented and greater than 2000 patients successfully screened through SMP2 over the past two years. QC fail rates have significantly reduced, as optimum sample selection improved throughout the network. CNVs and SVs called by NGS showed good concordance with FISH, although low tumour content and poor quality samples could result in low level CNVs being missed. Preliminary analysis indicates prevalence and distribution of SNVs consistent with published reports, including 33.5% KRAS and 16.1% EGFR mutations. The SMP2 testing panel has enabled the recruitment of > 150 patients to NLMT, with 31% of samples sent for screening eligible for one of 20 biomarker-specific NLMT cohorts, which rises to 51% when the immunotherapy arm is included. Conclusions: Delivering a nationwide screening programme within the NHS has raised a number of challenges across the entire patient and sample pathway: from patient recruitment, to sample preparation, right the way through to analysis of the results. Lessons learned will now enable informed updates to the NGS panel and analysis pipeline. Together with improvements to pre-analytical sample processes, this will ultimately increase the number of molecularly eligible patients that can benefit from novel targeted therapies. Clinical trial identification: The National Lung Matrix Trial Legal entity responsible for the study: NA Funding: Cancer Research UK with support from partners AstraZeneca and Pfizer, and in collaboration with Illumina. Disclosure: All authors have declared no conflicts of interest.

83: Improving the Cancer Research UK Stratified Medicine Programme 2 (CRUK-SMP2) pathway: an audit in Cardiff and Vale University Health Board (CAVUHB)

83: Improving the Cancer Research UK Stratified Medicine Programme 2 (CRUK-SMP2) pathway: an audit in Cardiff and Vale University Health Board (CAVUHB)

55 The introduction of the Cancer Research UK Stratified Medicine Programme 2 (CRUK SMP2) in North East England; lessons learned and experience gained

Introduction: The CRUK SMP2 programme was set-up to evaluate the feasibility of performing large scale molecular analysis within the NHS on the (often small) diagnostic biopsies obtained in NSCLC. The results are used to allocate patients to an appropriate molecular therapy within the “umbrella” MATRIX trial. Newcastle opened SMP2 on 01/10/2014. Here we report our first year’s experience. Methods: NSCLC patients with PS 0–2 were consented onto the CRUK SMP2. Matched residual diagnostic tissue and blood were sent to All Wales Genetics Laboratory, Cardiff. Samples with >70ng DNA were assessed for 28 oncogenes using Next Genuine Sequencing on the Illumina SMP2 panel. Results: 116 patients were consented from 6/10/14–1/10/15 referred from 12 oncologists. The data on patient/sample flow is shown in Fig 1. Median survival was 161 days from consent. The 1st sample was sent to Cardiff on 28/1/15 as the Illumina panel was undergoing fi- nal validation. 50 samples have been sent; 11 had insufficient DNA; these samples had lower cell number (but with no impact of necrosis/tumour proportion); The most commonly altered gene was K-Ras (13 of 22 adenocarcinomas). Only 2 patients with results from >25 of the 28 genes had no tier 1 or 2 ie potentially treatable molecular abnormalities. The median time from consent to result was 109 days (range 45–250) with delays occurring throughout the pathway. Conclusion: Patients and oncologists are keen to be involved in molecular profiling; but patients need to be consented early to allow results to guide therapy. Prioritisation of samples is key. Not all samples are suitable for analysis due to small cell number or low tumour proportion. Molecular analysis may require extra resource in pathology, if it is to become standard of care. The first 4 patients to start treatment on MATRIX were enrolled from 27/8/15 in Newcastle. Disclosure: All authors have declared no conflicts of interest.

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC. 38344105.

Olaparib Recommendations for Ovarian Cancer Patients

Peter Johnson speaks to Gemma Westcott, Commissioning Editor: Peter Johnson is Professor of Medical Oncology at the University of Southampton and Chief Clinician for Cancer Research UK. He graduated from Cambridge University and St Thomas's Medical School (UK). He trained in oncology at St Bartholomew's Hospital, London, where he was an Imperial Cancer Research Fund (ICRF) Clinical Research Fellow and completed his doctoral research on the Bcl-2 gene, its potential as a therapeutic target in lymphoma and the effects of CD40 ligation on the B-cell surface. He was subsequently a Senior Lecturer in Medical Oncology in the ICRF Cancer Medicine Research Unit, Leeds and took up the Chair of Medical Oncology in Southampton (UK) in 1998. He is responsible for bringing together a broad multidisciplinary group of basic, translational and clinical researchers, and linking the research of the academic unit to the extensive clinical practice in cancer treatment in the Southampton Cancer Centre. His research interests are in applied immunology and immunotherapy, lymphoma biology and clinical trials. He is Chief Investigator for lymphoma trials ranging from first in man novel antibody therapeutics to international randomized studies, and for the Cancer Research UK Stratified Medicine Programme. He was Chair of the UK National Cancer Research Institute Lymphoma Group from 2005 to 2011 and has been a member of national trials committees for the Medical Research Council, Cancer Research UK and Leukaemia and Lymphoma Research.

A collaborative approach to enabling stratified cancer medicine in the UK

Embedding stratified cancer medicine into the patient pathway will require adaptation of the diagnostic pathway to incorporate predictive molecular analysis, presenting challenges of accessing tumour samples of sufficient quality and quantity for analysis and ensuring the timeliness, accuracy, and clinical validity of results. In 2010, Cancer Research UK (CRUK), in partnership with AstraZeneca and Pfizer, set up the Stratified Medicine Programme (SMP1) to work collaboratively with a small number of hospital and genetics laboratories to demonstrate the feasibility of testing large volumes of samples, while working towards more standardised and efficient processes. By June 2013, 9010 patient samples had been sent for genetic testing and here we present an overview of our experience and the wealth of insights that have been generated into the complexities of attempting this transformation of National Health Service (NHS) care.

529 The Cancer Research UK Stratified Medicine Programme: From national screening to national trial

Background: The increasing demand for analysis of multiple predictive genetic markers in tumour samples to guide therapeutic decision-making requires the rapid validation and uptake of new knowledge and technology, as well as collaboration between clinical teams, cellular pathology and molecular genetics laboratories. Material and Methods: Between 2011 and 2013, formalin-fixed paraffinembedded tumour samples from patients consented through a network of hospitals underwent targeted mutation analysis. This was initially performed using Sanger sequencing and similar methods but following cross-validation an amplicon-based targeted next generation sequencing panel was implemented. Clinical information based on the requirements of the national cancer registration dataset was also centrally collated for each participant. The current second phase of the initiative has a sole focus on patients with advanced lung cancer, and aims to expand the geographical reach to perform molecular pre-screening of samples to help determine patient eligibility for the National Lung Matrix Trial, a multi-arm stratified phase II clinical trial of novel therapeutics. Results: 10,754 patients (98% of those approached) consented to analysis of material during phase one, with 9010 samples submitted for analysis. The table shows the overall results of analysis for the first 7850 samples. Analysis by histological subtype enriches for certain mutations, with 925 pulmonary adenocarcinomas showing 36.5% KRAS mutations, 11.6% EGFR mutations and 2.5% ALK gene rearrangements and 56 mucinous colorectal adenocarcinomas showing 43.5% BRAF mutations and 50% KRAS mutations. Conclusions: A centralised national testing network for genetic analysis of formalin-fixed paraffin-embedded tumour samples is feasible and acceptable to patients and clinicians, with applications beyond genotyping for currently licensed oncologic therapies. Acknowledgements: Funding for the Stratified Medicine Programme is acknowledged from Cancer Research UK and programme founding partners AstraZeneca and Pfizer.

IS7–4 - Personalised Medicine: The UK Experience

‘Personalised medicine’ means tailoring cancer treatment very precisely to an individual person's cancer. Somatic mutation testing in patients with solid tumours is already happening and demand is predicted to increase, but published data suggest there are issues with the reproducibility and accuracy of results; for widespread use, techniques should preferably work in formalin-fixed, paraffin embedded tissue. Cancer Research UK set up a national programme, Stratified Medicine Programme (SMP) to test whether this was possible and to provide the foundations for a future national service. Phase I of the SMP was conducted in 8 Experimental Cancer Medicine Centres (ECMCS) across the UK, between September and June 2013. The aim was to collect and analyse up to 9,000 tumour and corresponding blood samples from breast (PIK3CA, TP53, BRAF, PTEN mutation and PTEN LOH by microsatellite analysis), prostate (PTEN and BRAF mutation, TMPRSS2-ERG fusion by FISH BUT moving to rt-PCR, and PTEN LOH by microsatellite analysis), lung (EGFR, KRAS, BRAF mutation and ALK rearrangement by FISH), ovary (TP53, PTEN, PIK3CA and BRAF mutation and PTEN LOH by microsatellite analysis) and colorectal (KRAS, BRAF, NRAS, PIK3CA, TP53) cancer and melanoma (PTEN and BRAF mutation, TMPRSS2-ERG fusion by FISH but moving to rt-PCR, and PTEN LOH by microsatellite analysis) to be sent from the Clinical Hubs to Technology Hubs for testing; the results were then to be fed back to the Clinical Hubs. In Leeds we planned to collect tumour/blood samples from patients with breast cancer (350 patients), ovarian cancer (250), colorectal cancer (150) and melanoma (150). Internal processes were set up to collect all these samples in collaboration with the corresponding clinical, medical, pathology and phlebotomy/clinical biochemistry teams and where possible in alignment with routine clinical practice or existing research needs; these tissues samples were sent to the Royal Marsden Technology Hub for analysis. The mutational analysis results were then returned to the Clinical Hubs and linked to an electronic patient information data set. The national programme was completed successfully. We are now setting up Phase II, focussing on patients with lung cancer with a view to their inclusion in trials of novel targeted agents.

Utilizing a collaborative working model to optimize molecular analysis of solid tumors in the Cancer Research UK's Stratified Medicine Programme.

11094 Background: The Stratified Medicine Programme is demonstrating large scale molecular testing of solid tumours in the UK using a range of technologies. The collaborative model has allowed three laboratories to share and compare data on mutation frequencies including mutation exclusivity, test turnaround times and failure rates, to inform a future routine service for clinical care. Methods: Phase One is a two-year pilot study of molecular analysis of surplus diagnostic FFPE tumour tissue obtained from patients with cancer of the breast, colorectum, lung, ovary, prostate or malignant melanoma. Samples are tested for specified genes of clinical and research interest (for example KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT). The labs have developed and validated protocols with comparable sensitivity for the simultaneous molecular analysis of multiple genes. Results: By 31 December 2012, 4,734 sets of molecular results were completed with 60% of tumour-site specific reports issued within the target 15 days (from sample receipt). Failure rates vary with both sample quality and the type of analysis performed. The Table illustrates the link between turnaround times and failure rates, showing that repeat testing for specimens which initially fail may reduce overall failure rates but consequently increase average turnaround times. Conclusions: We will report comparative data across the three testing labs and identify multiple factors that affect mutation detection rates, failure rates, turnaround times and reporting procedures. The Stratified Medicine Programme acknowledges funding from Cancer Research UK, AstraZeneca, and Pfizer. [Table: see text]

P4.01 Delivery of High Quality Molecular Panel Tests for 9,000 Cancer Patients Routinely Consented for Use of Molecular and Clinical Data

ABSTRACT Background Molecular analysis of tumours may be used to identify patients predicted to benefit from targeted therapies. The Cancer Research UK Stratified Medicine programme is piloting plans to apply testing broadly across the UK healthcare system, linking molecular phenotype to clinical outcomes enabling further research and cohort identification of patients. Methods The Stratified Medicine Programme has been developed in partnership with Astra Zeneca, Pfizer, the UK Department of Health and academic researchers. Phase One is a two year feasibility study to demonstrate the collection and molecular analysis of consented sections of surplus diagnostic tumour tissue and blood samples from 9,000 patients across a network of 20 hospitals.Samples are tested for mutations in genes of potential clinical interest (KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS-ERG, EGFR, EML4-ALK and KIT). Different technologies are used across the three testing laboratories but all tests are technically validated with external quality assurance monitoring and targets for completion in clinically relevant timescales. Data (diagnostic including molecular information, treatment and clinical outcome) is collected through existing hospital systems, and transferred to a central data repository hosted within the Eastern Cancer Registry Information Centre. Results The study opened in September 2011 with 2160 patients consented to participate by April 2012, 607 sets of molecular results returned and planned accrual rates for Year One met (300 samples/month). Test requests and reports are exchanged electronically with standardisation of reporting being developed. Partnerships with two clinical trials for pre-screening of cohorts have been agreed.Programme accrual by tumour type. Conclusions We will report the emerging results, observations of processes and potential issues identified in delivering a scalable model for routine, high quality, prospective molecular characterisation of tumours for cancer patients, with consent for the collection, storage and research use of population-scale genetic and outcomes data. Table 1 . Programme accrual by tumour type Year one targets Patients consented Breast 641 455 Colorectal 644 263 Lung 641 610 Melanoma 213 150 Ovary 200 132 Prostate 660 529

Emerging findings in the Cancer Research UK stratified medicine program.

TPS10633^ Background: Molecular analysis of tumours may be used to identify those predicted to benefit from novel targeted therapies. The Cancer Research UK programme is piloting plans to apply such testing broadly across the UK healthcare system, linking molecular phenotype to clinical outcomes. Methods: The Stratified Medicine Programme (SMP) aims to develop a model for high quality, large-scale molecular characterization of cancer specimens through an initiative developed in partnership with AstraZeneca, Pfizer, the UK Department of Health and academic researchers. Phase One of the SMP is a two year feasibility study. It aims to demonstrate the submission of consented blood samples and sections of surplus diagnostic formalin-fixed paraffin-embedded tumour tissue from 9,000 patients at centres across the UK to one of three ‘technology hubs’ for mutation testing of genes of potential clinical interest (KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT) in six selected tumour types. The tests are technically validated and will be completed in clinically relevant timescales. Data including pathological and treatment information and clinical outcome is also collected for the recruited patients, linked to the genetic data and stored in a central data repository hosted within the National Cancer Registration Service. The study opened in September 2011 at 7 sites across the UK and by the end of 2011, 760 patientswith breast, lung, prostate, colorectal, ovarian cancer or metastatic malignant melanoma had consented to participate. 142 sets of molecular results had been returned to clinical teams. Updated figures will be presented at the meeting, by which time the programme is projected to have accrued 4000 subjects. By 2013, we hope to have developed a scalable model for routine, high quality, prospective molecular characterisation of tumours for NHS cancer patients, with consent for the collection, storage and research use of population-scale genetic and clinical outcome data. We will report the emerging results from the Stratified Medicines Programme and early insights into implications for wider implementation across the UK healthcare system.