A new ESMO scale for DNA mutations: ensuring targeted cancer drugs reach the right patients

An image to illustrate tumour dna and cancer drugs
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Cancer specialist Professor Fabrice André tells SciTech Europa why a new ESMO scale for DNA mutations in cancer cells should be included in test reports so that patients are accurately matched to targeted cancer drugs and treatment is more cost effective.

Testing cancer cells for DNA mutations is rapidly becoming a routine part of diagnosis and follow-up for thousands of people with breast, lung, blood, and other types of cancer, and a growing proportion of patients are being offered targeted treatment based on the results. This approach of tailoring treatment to the genetic characteristics of an individual’s cancer – an example of precision medicine – is significantly improving the outlook for people with the disease and raising expectations amongst doctors and patients alike.

However, the increasingly complex tumour DNA mutation profiles revealed by advanced gene sequencing techniques is making it more and more difficult to translate data into optimal treatment decisions. For this reason, the European Society for Medical Oncology (ESMO) has supported the development of a scale, called ESCAT (ESMO Scale for Clinical Actionability of molecular Targets), to simplify and standardise the interpretation of results and enhance patient care.

Professor Fabrice André, Chair of the group of leading cancer experts in Europe and North America that initiated the project, spoke to SciTech Europa about the importance of integrating the scale into routine clinical practice.

What are the main problems in interpreting information about the DNA mutations in a patient’s cancer?

In a way, we are the victims of our own success. Following recent technological advances in genetic profiling, we can now request dozens of genes in tissue or liquid biopsy samples from a patient with cancer to be tested for many different types of mutation. A report is then sent to the doctor and patient listing the mutations but currently gives no guidance about whether a specific mutation is important for that patient’s type of cancer, and if it has been validated or is still being researched. As a result, there is a very real danger that the doctor may prescribe a medicine aimed at targeting a mutation that is not relevant for that patient when a conventional therapy may be more appropriate, or the patient should be referred for inclusion in a clinical trial.

There is also the aspect of cost effectiveness. The new targeted medicines are expensive and, with limited budgets, it is important that we prescribe them for patients most likely to benefit in order to optimise the use of resources for cancer care across communities.

How will ESCAT help doctors and patients make treatment decisions?

The scale provides guidance to doctors on how to interpret the results of multigene testing in a realistic way and avoid over-interpretation. It helps them distinguish between alterations in tumour DNA that are important for decisions about targeted medicines or access to clinical trials, and those which are not relevant. It also makes it easier for doctors and patients to discuss the results of multigene sequencing and agree the right treatment for the right patient.

For the first time, we have a tool that makes it clear what data are needed for a mutation to be actionable and how this may change in response to new clinical data. It simplifies and standardises choices about targeted treatment so that patients can receive the same evidence-based advice wherever they are treated.

We know that precision medicine is spreading from highly specialist cancer units to other healthcare facilities so more patients can benefit. This is a huge leap forward from what was being achieved even in academic centres just a few years ago, when perhaps one in 10 patients were enrolled in clinical trials of targeted treatment on the basis of tumour DNA alterations.

The genie is well and truly out of the bottle. As precision medicine spreads quite rightly from specialist centres to community-based services over the next few years, ESCAT can bring order to the current jungle of mutation analysis. It will enable us all to speak the same language for classifying mutations and prioritising how we use them to enhance patient care.

How do you plan to disseminate the scale, given that you cannot make it mandatory for everyone to use it?

In developing ESCAT, ESMO brought together the best experts in the world within this field so that we truly have a scale about which there is excellent agreement. We are disseminating information about ESCAT in order to convince all stakeholders involved in DNA profiling to endorse the scale and integrate it into test reports sent to clinicians. As a first step, we want all cancer researchers to use it in clinical trials so that it becomes as familiar to clinicians as traditional measures of cancer grade and stage.

It is essential that clinicians receiving tumour DNA reports understand the use of ESCAT, and we are providing educational opportunities for clinicians about the value and relevance of this information to the treatment of their patients.

Stakeholders are not only those in the laboratories carrying out DNA sequencing on tumour samples and clinicians who receive the results. They are all the people involved in developing cancer services, agreeing access to targeted cancer medicines, and initiating and co-ordinating research programmes. We need to reach them too, demonstrating the importance of ESCAT in helping to ensure that money provided for tumour testing and targeted therapies is well spent.

In the future, patient advocacy groups may also play a role in ensuring a wider understanding of the importance of ESCAT by all those living with cancer and undergoing tumour DNA profiling to guide therapy.

However, at present, our focus is on bringing order to the rapidly changing application of multigene testing, and to the interpretation of results by scientists and clinicians involved in treatment decisions.

Isn’t ESCAT adding an extra level of complexity or delay in decision-making?

No, there is a clear need for this scale. Simply knowing that a patient’s cancer has one or more mutations is not enough. What is important is whether one or more of those mutations are actionable with drugs that are already available or being tested in clinical trials. The scientists who carry out multigene sequencing are not suggesting that every DNA mutation they identify is actionable. Like those of us who are clinicians, they want to ensure that patients whose mutations are actionable get the most effective treatment. We don’t expect testing to lead to targeted treatment in all of our patients. Even if a positive result leads to effective treatment in 10-20% of patients, that will be a big success. I believe that all stakeholders will welcome ESCAT in enhancing the value of multigene testing for guiding appropriate treatment for our patients – whether that is the latest targeted drugs or more conventional therapies.

Professor Fabrice André
Chair, Translational Research and Precision Medicine Working Group
European Society for Medical Oncology (ESMO)
Professor of Medical Oncology
Institut Gustave Roussy
Tweet @myESMO @FAndreMD
www.esmo.org/Policy/ESCAT

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