Perfecting personalised medicine in cancer research

  • Every targeted therapy should focus on well-defined and reliably-detected patient populations, potentially pathology-agnostic.

  • Any potential flaw in the screening process decreases the efficiency of clinical trial enrolment.

  • The platform supports molecular-based translational research and biomarker discovery with the ultimate aim of proposing new therapeutic options for patients.

Marie Morfouace and Davi Kaur, of the European Organisation for Research and Treatment of Cancer (EORTC), outline some of the challenges faced in attaining the best screening for precision medicine trials and what the EORTC is doing to address them.

Healthcare is rapidlymoving away from one-size-fits-all and transforming into personalised (or precision) medicine, where specific biological markers are identified, helping to determine the best treatment for each patient. However, even with this rapid progress, clinicians still prescribe therapies based on population averages or broad patient subgroups, delivering care which is ineffective in a significant proportion of patients.

Timelines are shortening in clinical research, resulting in many drugs going into clinical trials without appropriate understanding of the biology or without adequately-evaluated biomarkers. This means they fail at a later stage and consequently there are high rates of drug attrition.

With precision medicine, every targeted therapy should focus on well-defined and reliably-detected patient populations, potentially pathology-agnostic. The necessary clinical trials face their own sets of challenges, such as the need to screen a large number of patients in order to be able to enrol the population of interest, since most molecular biomarkers have a low prevalence in cancer. Any potential flaw in the screening process decreases the efficiency of clinical trial enrolment and reduces the probability of reliable results. Therefore, selection of patients should be made on validated biomarkers resulting from quality-assured infrastructures.

Screening platform

To ensure quality for precision medicine trials, the European Organisation for Research and Treatment of Cancer (EORTC) established the SPECTA screening platform. This is a translational research infrastructure that provides a quality-assured European platform for collecting biological material from cancer patients. The goal of the platform is to support molecular-based translational research and biomarker discovery and, ultimately, to propose new therapeutic options for patients.

Clinical trials evaluating new treatments or diagnostic features can be added into the SPECTA platform. Then registered patients can participate in clinical trials investigating therapies that match their molecular profiles.

The Integrated Biobank of Luxembourg (IBBL) is the EORTC-designated laboratory responsible for the biobanking and quality control of all human biological material. IBBL and EORTC are setting up a digital pathology platform for central pathology review. Molecular analyses are performed by accredited laboratories, using validated tests, including, but not limited to, the Illumina TST-170 or FoundationOne.

So far, over 1,000 colorectal cancer patients and 500 lung cancer patients have been enrolled in SPECTA. EORTC-SPECTA is also a partner of the European Reference Network for rare cancers. This network uses SPECTA as its main platform for translational research.

In the US, the National Cancer Institute (NCI) is conducting a trial called NCI MATCH, whereby patients with advanced solid and blood tumours are assigned to receive treatment based on the molecular profile of their tumours, as assessed with genomic sequencing and other tests. Independently of the tumour type, the enrolment of a patient into an arm of the MATCH trial is solely based on tumour molecular alterations. The trial seeks to determine whether treating cancer based on these specific genetic changes is effective and to gather enough scientific evidence to push the concept of precision medicine into clinical practice.

The right patient in the right trial

For example, for gynaecologic cancers, the MATCH trial has 24 arms open. However, even with such a high number, only 23% of patients were matched to a drug and enrolled in the trial (Barroilhet and Matulonis, Gynecol Oncol, 2018). This highlights the need for a robust screening infrastructure, validated biomarkers and quality-controlled processes to ensure that the right patient is enrolled in the right trial.

The challenge faced with these types of platform is to develop an infrastructure through an appropriate and rigorous regulatory framework. The terms ‘precision medicine’ or ‘personalised medicine’ are generally understood to refer to a medical model that uses the characterisation of individuals’ phenotypes and genotypes for a tailored therapeutic strategy. To make this approach work in routine practice, the development of complex biomarker assays is required (Salgado et al, Eur J Cancer, 2017).

The 2016 Innovation in Biomarkers in Cancer Drug Development meeting, which involved stakeholders from academia, industry, regulatory bodies and governments, produced a number of critical points and consensus recommendations on the development and implementation of biomarkers. In summary, questions were raised on assays and technologies entering daily practice with proper validation; there is a lack of standardised tissue collection processes. It was emphasised that before any assay is offered to the healthcare community, it needs to have a proven clinical utility. A proper regulatory framework needs to be established and precision medicine should be available to all and not just a select few that can afford it.

About the Authors

Marie Morfouace isthe Translational Research scientist, based in the TR unit at EORTCHeadquarters, Brussels, Belgium. She received her PhD from Nantes University and then moved to Memphis in the USA to complete her postdoctorate work, focusing on translational research in paediatric neuro-oncology. She then joined CRUK as a senior scientist where she focused drug discovery. She is now the translational research scientist at EORTC, actively working on the SPECTA programme.

Davi Kaur is the head of Communication for EORTC. She graduated from the University of Wales College of Cardiff in 1993 with an Honorary Degree in Applied Biology. She completed a Masters in Philosophy at the Institute of Nephrology at University of Wales College of Medicine, where her research focused on the effects of peritoneal dialysis fluid on inflammation.

Don’t miss your complimentary subscription to Deep Dive and our newsletter

Sign up



Your name

Your e-mail

Name receiver

E-mail address receiver

Your message