Progress of personalised oncology treatment

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Published: 22 Oct 2012
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Prof Martine Piccart – President-Elect of ECCO

ECCO President-Elect Prof. Martine Piccart warns that although there has been rapid progress in development of personalised cancer treatment, there is still a shortage of diagnostic tests and effective prognostic biomarkers to identify which patients will respond to treatments or will eventually relapse.


Without this, oncologists will continue to over-treat many patients and waste valuable resources. Prof; Piccart concludes by commenting that personalised medicine is currently simply stratified medicine and explains what progress must be made in order for personalised medicine to be realized to the full.

Martine Piccart, thank you very much indeed for talking to the ECCO topic today which is personalised medicine. You’re giving a lecture on how personalised medicine has impacted on all areas of the medicine field which is called oncology. You’re also going to talk about a number of barricades, a number of pitfalls, electric fences. Tell me first of all about your favourite topic, early breast cancer.
Yes indeed. I decided to take early breast cancer as an example to try to show people what kind of progress we have really made towards personalised medicine but what also are the remaining barriers to be really able to offer individualised therapy to each woman with early breast cancer. So essentially my message is that there has been significant progress in the tailoring of local regional therapy for early breast cancer with many women enjoying breast conservation, the sentinel node technique, instead of radical mastectomy with full axillary dissection. I’m also pointing to the fact that selected women can also enjoy a one day treatment for radiotherapy instead of a 5-6 week treatment and explaining that this is the result of the vision of a few individuals who have had the courage to break from tradition, to follow-up with their ideas, to build the clinical trials necessary to convince the scientific community.
So there I think we have done substantial progress. There are still problems to be solved, for example it’s very difficult for surgeons and radiotherapists doing clinical trials to find the necessary funding to examine, for example, the reasons why some carefully selected women undergoing these less aggressive local regional therapies will nevertheless present with a local relapse. So there is the need there to really do translational research in the surgical and radiotherapy trials and it’s very difficult to find the money for doing this kind of research today.
Now, in the field of medical treatment, my own view is that we are in the era of stratified medicine and not personalised medicine. So I’m going to show two examples. The first one is, of course, the need for prognostic biomarkers. We need to be able to identify women with gentle tumours who are not going to relapse, who are essentially cured by surgery and radiotherapy. This is very difficult. The traditional diagnostic tests that we use which are in the hands of pathologists are very suboptimal. The result is a very high degree of overtreatment of women presenting with small breast cancers and no involvement of nodes. Many of these women undergo chemotherapy and probably don’t need it. Then I am explaining a little bit how difficult it is in Europe to promote novel, more powerful diagnostic tests and I am just explaining the story of MammaPrint which is a multigene prognostic signature and which is not yet on the  market in Europe while in the United States a very similar signature, Oncotype DX, is now prescribed by 60% of oncologists in spite of the fact that they are also waiting in the United States for the results of a large clinical trial, TAILORx, that should establish the definitive clinical utility of the signature. In Europe we are also waiting for the results of the MINDACT trial expected for 2015 but the test is not prescribed by oncologists in Europe. So there is a difference in culture there; it looks like in Europe we don’t pay enough attention to the importance of diagnostics. I think there cannot be precision medicine without powerful diagnostic tests.
So it’s not just about genomes and targeted clever medicines to individualise medical treatment, it’s about surgery and doing the least damage possible. It’s about radiation, although they could use also some genes like the hypoxia genes. It’s about money to do tests which are not so fashionable and trials which are not going to help anybody except the patient.
Exactly, these trials are very hard to do.
And this needs an initiative from government; pharma and industry are never going to do this. And it needs patients to start demanding this. Personalised medicine is not yet, in your view, further than stratified medicine in medical oncology.
Yes, I think a very good example is the story of trastuzumab. So trastuzumab is a targeted drug that helps one in five women with breast cancer. These cancers over-express the HER2 protein and trastuzumab is the antibody that targets this receptor. So the treatment is clearly working, it is saving lives, it is expensive. It costs about €34,000 to give one year of adjuvant trastuzumab to women with early breast cancer. OK, so my problem is that very little is done, for example, to secure the diagnostic test that allows the oncologist to prescribe this drug. So this is the HER2 status of the breast tumour. We know today that there are false positive tests in the range of 15%, this is what we have discovered in clinical trials with central pathology control. So that is astonishing to me, it means that a lot of women in Europe are getting this treatment and should not get it.
Spending money which could be saved.
Absolutely but not enough attention is paid to the diagnostic test. Then there is another problem - we know that even if the target is there, even if the tumour is over-expressing this receptor, trastuzumab will work 50% of the time. In the other 50% the cancer cell is clever and will find an escape mechanism. There has been very little support given when we did conduct the registration trial of trastuzumab to really collect the tumour blocks, to analyse the blocks, to try to understand who are these women who in spite of getting trastuzumab experience a relapse. So we are nowhere with the biomarkers telling us if a patient will or will not benefit. Why? Because the funding for this translational research only came from the pharmaceutical industry partner and was totally insufficient. So again this is calling for more investment by governments in translational research at a critical point in time. I think the critical point in time is the large registration study that is going to bring the drug on the market, there you have an obligation, I think, to do excellent research. Now the technologies are even better than they were ten years ago, they are more sophisticated but they are also, if there is no co-ordination in Europe, I am afraid that the next ten years will see duplication of efforts with all kinds of platforms being built everywhere and no dialogue occurring between the researchers.
I think you’ve made some very, very important points, particularly for this ECCO conference because here we’ve got the clinicians, we’ve got the patients, we’ve got the government and we’ve got regulators and we’ve got pharma. So we should be coming out of this discussion with some solutions, for instance if pharma won’t fund research in Europe because European regulators are so slow in coming to the decision on allowing something to come out and getting money back into the pharma then we’re going to be here talking about this in ten years’ time with no change.
I fully agree.
Thank you very much indeed, I appreciate it.
Thank you Gordon.