Personalisation of cancer care, by prescribing drugs that target specific mutations in patients' tumours, is already a reality. For a subset of patients with non-small cell lung cancer (NSCLC) and whose tumours have a mutation in a gene called EGFR, targeted therapies are available.

To prescribe these therapies, called tyrosine kinase inhibitors (TKIs), a genetic test is needed on the tumour tissue. However, the challenges of obtaining tumour material via biopsy means that some patients are not able to have the required tests. 

Tests that analyse the circulating tumour DNA of these patients for mutations in EGFR are already being delivered by a select group of laboratories in the NHS, thus increasing access to these targeted therapies. 

This second ctDNA briefing note focuses on how ctDNA testing is being used to inform treatment decisions for lung cancer patients but also outlines some of the challenges that need to be managed when using this technology. 

Lung cancer comes out of the shadows

For a long time lung cancer was a Cinderella cancer, with a poor outlook and stubbornly low survival rates. Advocacy by patient groups and charities, combined with a boost to scientific and clinical research funding for new treatment approaches, are beginning to have an impact but will take time to come to fruition. 

The current situation in terms of the depth and breadth of lung cancer research, and the progress that is being made, is encouraging. Among the wide range of clinical trials currently running, are: the Lung Matrix Trial, which is matching patients to drugs according to the genetic make-up of their tumour; LUCID, looking at technology that could diagnose lung cancer from compounds exhaled in the breath; or TRACERx, which is studying the genetics and other features of NSCLC to determine how they change through time. 

Pioneering ctDNA testing in lung cancer

It seems appropriate that patients with NSCLC are the first to benefit from the relatively new technology of ctDNA testing on the NHS. The suitability of lung cancer is due to: 

  • Availability of targeted therapies that require a companion diagnostic genetic test, which can be carried out on solid tumour material or on blood plasma. ctDNA testing can be used at different stages – to aid prescription decisions for first line TKIs (10-15% of tested patients have the mutation), and to detect emergence of a resistance mutation to these drugs, T790M, allowing a second line TKI therapy to be tried (the mutation is found in around 50% of patients tested).
  • Clinical need, where difficulty in obtaining enough solid material for a genetic test is restricting access.
  • Techniques that reliably detect ctDNA in lung cancer are readily available. 

The total number of patients eligible for these tests is small – around 15% of the patients diagnosed with lung cancer each year. Of this group, an even smaller proportion will have EGFR mutations and be prescribed therapy. This can be seen as an advantage – the small numbers of tests required means that laboratories do not have a sudden significant increase in workload, can refine techniques, train staff, and determine how best to incorporate these tests into the work of their laboratory. Although these tests only currently benefit a minority their use represents an important advance in terms of adopting and using innovative technologies on the NHS, for patient benefit. 

Making the most of ctDNA technologies

The PHG Foundation held a workshop at the end of February, bringing together laboratories, clinicians, pharmaceutical companies and policy makers with an interest in the development, use and promotion of ctDNA testing in lung cancer. During the talks and discussion sessions the group explored the issues affecting the implementation of services, with a particular focus on three questions: 

  1. Clinical utility: what are the key challenges across the patient pathway?
  2. Clinical utility: what further evidence is needed in advance of further implementation?
  3. Service infrastructure: how will testing fit into cancer services? 

The group also touched on how the use of ctDNA testing can be expanded: for example, could the technology be used to triage patients for more expensive tests such as CT scans?

That the technology is ready for prime-time was widely agreed but, as was acknowledged, there are information gaps, particularly in terms of guidelines about the best time to test and what negative test results mean. The need for awareness, information and education arose time and again during the day as did the question of how to ensure that ctDNA testing is equitably available, for all patients. 

A liquid testing future?

ctDNA clinical research is fast-moving, dynamic and already benefiting patients. The wealth of clinical trials underway, along with these pioneering ctDNA services, will soon give answers to many of the questions that arose at the workshop. ctDNA testing is here to stay and over the next couple of months PHG Foundation will explore the issues raised at the workshop in more depth. We will  also consider the bigger picture in terms of how ctDNA testing could benefit cancer care further, not only in lung cancer, but also in other cancers.