Alastair Greystoke joined Newcastle University and the Northern Centre for Cancer Care, in Newcastle upon Tyne, UK, in 2014 after completing his PhD and 8 years’ work at the University of Manchester and The Christie NHS Foundation Trust in Manchester, UK. He is one of three consultants who run the Sir Bobby Robson Cancer Trials Research Centre at the Freeman Hospital in Newcastle upon Tyne and has a special interest in the development of new anticancer drugs for patients with thoracic malignancies.
In addition to being a Senior Lecturer in Medical Oncology, Doctor Greystoke is Joint Chief Investigator of the CONCORDE study (adding new drugs to radical radiotherapy for non-small-cell lung cancer) and Clinical Lead for Cancer at the Yorkshire and North East Genomic Laboratory Hub and leads the pharmacodynamic biomarker team at the Northern Institute for Cancer Research at Newcastle University.
Join Alastair in our interactive virtual discussion: Promises and pitfalls of precision medicine clinical trials, now and in the future by clicking here.
FLG: Can you give us an introduction to yourself and the work that you do?
Alastair: I am a senior lecturer and honorary consultant at Newcastle Hospitals Trust. I work on the Sir Bobby Robson unit, which is our Phase I drug development unit. I have a special interest in early drug development, particularly for thoracic malignancies and we run a portfolio of precision medicine clinical trials aiming to match patients to genomic targeted therapies.
FLG: As technology moves forward, people think that because we can do whole genome sequencing, we should always be doing that. What are your thoughts on this and why would you choose to use other technologies?
Alastair: When you sequence the whole genome, you will commonly find multiple abnormalities, and that can actually lead to additional problems. One can be working out what the primary driver is in that patient for cancer, and what may be most likely to respond to targeted therapy. You can also find incidental findings that can be unexpected, both in terms of the cancers genomics but also unrelated to the cancer, and this may have implications both for them and their families health.
There are also a number of patients’ tumours that may not be suitable for whole-genome sequencing, however where you may be able to get the answer using a simpler technique. This could a small next-generation sequencing panel aimed at abnormalities that you can target or using a liquid biopsy on circulating free DNA which may give you a more rapid result and enable you to match the patient up with appropriate targeted treatment.
FLG: There is a growing interest in carrier typing to understand complex rearrangements and fusion products, has this piqued your interest?
Alastair: I think some of the most targetable oncogenes are fusions, the number of those are relatively small but you don’t want to miss these because if you have an approrpiate medication for that – those are some of the most targetable abnormalities that we have.
In terms of complex carrier types, we know that this is a mechanism of resistance to chemotherapy and may be a mechanism of resistance to other drugs – whether we can actually target those abnormalities is still a subject of research.
FLG: We know that COVID-19 has affected cancer care in a number of ways, from people not showing up to appointments to clinical appointments being carried out virtually. How has it affected the clinical trials?
Alastair: It has had a massive impact on clinical trials.
A number of centres have had to close recruitment to clinical trials, we saw data presented at ASCO showing recruitment in America to cancer trials dropped by approximately 50%, and I think we will see a similar or worse impact in the UK.
For patients who are already on studies, we have been doing our very best to carry on looking after them and ensure their safety but we have had to miss out on some supernumerary visits, and scans have been put back, which may make it more difficult to interpret the final results from some of the trials that have been running.
There will also be a delay in setting up new trials because both the NHS, pharmaceutical companies and charities have had to rapidly respond to the COVID 19 situation, diverting attention from trial set-up and that is going to have an ongoing impact.
Lastly, and unfortunately, we were noticing already that we are saw fewer patients being diagnosed with cancer during the acute COVID 19 period, and now are starting to see the patients presenting with later-stage and more advanced disease disease, where they are less well, and may be less suitable to go on to a clinical trial.
FLG: Not all oncologists are keen to integrate genomics into their routine care – what do you think is needed to change their perceptions?
Alastair: It is education and experience.
They need to understand the process, what genomics is and what it has to offer. We have to be realistic and should not be giving inflated claims for what we can achieve with genomics. But if we show how it can improve patients care and how it can improve clinical trials, When clinicians see their patients benefiting from their approach, they will enthusiastically buy-in.
For this we need to teaching clinicians how to interpret genomic profiles and what they mean for their patients – then get access to appropriate treatment and they will see how that can benefit their patients.
FLG: What are you most excited about that is coming in the precision oncology space?
Alastair: Well, I obviously get very excited about lung cancer because that is what I treat day in day out. Of those, the two coming through most rapidly are RET and MET, I think the MET exon 14 skip lesions are particularly interesting because a lot of the other oncogenic abnormalities that we see tend to be in non-smokers, so that is a select population – non-smoking related lung cancer. While the MET exon 14 we certainly do see in smokers, and so that may be one of the first good targetable abnormalities in smoking-related lung cancer.
FLG: If there was more awareness of the precision oncology trials and how they are done, what do you think a clinician could stand to gain from this?
Alastair: I think there is still this perception that some of the early clinical trials and some of the new agents are just for patients who are at the end of a line, where there are no realistic treatment options left. Actually, for some of our patients, the entry on to a first-line clinical trial could be their best option. It could be better than an NHS approved treatment if they are getting standard chemotherapy from the NHS, and we have managed to identify a genomic abnormality where we have a promising medication for them to try. In ft a number of the targeted agents may actually work best in the 1st line setting.
