Dr Alastair Graystoke, Newcastle University
A new drug to combat one of the more aggressive forms of lung cancer has been approved by NICE - UKís the National institute for Health and Care excellence. Itís been developed at record-breaking speed by AstraZeneca and, in clinical trials, almost twice as many patients responded to the new agent, called osimertinib, compared with existing chemotherapy. Cancer specialist Alastair Graystoke, one of the investigators who has been testing the new agent, told Chris Smith how it works and who might benefitÖ
Alastair - Osimertinib is a new drug thatís become available for patients with a rare type of lung cancer. Itís lung cancer thatís got a mutation in a protein called epidermal growth factor receptor. This protein is like a switch that turns on and then drives the cellís growth, makes it grow, makes it spread, divide, cause symptoms to the patient and this tablet (Osimertinib) goes in and blocks that protein and stops the cells growing. The lung cancer cells seem to be addicted to this - what we call oncogene addiction - and so, if you can block this signalling, you actually see the cancers shrinking and patients feeling better with a better quality of life.
Chris - How do you work out who might benefit from it?
Alastair - When patients first have their lung cancer diagnosed, then they have their cancer checked for a mutation in this protein. They can then go on to drugs that we have had for about four or five years that target this protein, but they only work for about a year and then this cancer becomes resistant. So whatís neat about this new drug is weíve worked out how the cancer becomes resistant, and the answer to that is itís developed a secondary mutation in this protein that blocks the binding of the drugs we used to have.
So what AstraZeneca have done is develop a new drug that targets the new mutation, the new switch, and is very effective. The other really neat thing about this tablet is that, at the same time in the clinical trials where they were looking at biopsies, they were also doing blood tests to look for the presence of tumour DNA in the circulation. And they were able to show that if you can detect the tumour DNA in the circulation, itís just as good as doing a biopsy. So in fact, thereís some patients now who wonít need a biopsy - weíll just do a blood test and show this is how their cancer has become resistant and now we can give them this new tablet with a good chance of responding.
Chris - And when someone is started on this sort of therapy, what sort of outcomes are you seeing with it?
Alastair - So, in about seventy per cent of patients we see what we describe as a good shrinkage, which is their tumour volume decreasing by about half. In some of the patients weíve actually seen their cancer shrinking down so far that weíre having really difficult seeing it anymore. It doesnít work for everyone and, at the moment, weíre not really sure how long it works for but it seems to be about an average of a year and then the cancer can, unfortunately, become resistant again.
Chris - What about cancer that has spread to distant sites - metastasised to other parts of the body - does it work on those distant tumours as well?
Alastair - Most of my patients to have metastases; most of them present late with cancers that are already spread. But whatís really interesting about this drug as well is that itís very common for patients with this subtype of tumour for it to spread to the brain and the spinal cord, and this drug seems to work very well in that setting as well.
Chris - How much does it cost?
Alastair - So the list price is between four and five thousand pounds a month. Itís been made available to the NHS through the Cancer Drugs Fund because NICE didnít think that the data was mature enough; we donít know how long this tablet works for to work out if this is a cost effective treatment. So it has two years approval through the Cancer Drugs Fund and, hopefully, during that time we will develop enough data to show that it can improve patientís outcome, and that they do live longer, and that itís a cost effective treatment to use in the National Health Service.
Chris - Most of the cost, of course, comes from whatís involved in developing a new drug, isnít it - tell us about the story of the development of this one?
Alastair - Well, the nice thing about this is that, on average before itís taken about ten years to develop a drug through clinical trials and that ten year process, and the costs behind it, is one of the main reasons that the drugs are so expensive when they come out the other side.
This drug first went into patients in 2013, and it got licensed in the US in 2016, the UK 2016. So itís only three years from first time in man to us having access to it in the NHS. Now if we can do that for all our drugs, hopefully it will bring down the cost of drug development and bring down the costs when they come out the other side.
Chris - Why was it so quick?
Alastair - I think because there was a really nice scientific rationale: we knew what the basic science was; the drug is very effective; has relatively little in the way of side-effects. And thereís been new processes brought on by the FDA in America and the European Regulatory Authorities to fast track drugs like this which look to be very effective so we can give them to patients as soon as possible.