BACR & ECMC: Therapeutic interventions for cancer prevention
Surrogate endpoint biomarkers in research
Dr Bernardo Bonanni – European Institute of Oncology, Milan, Italy
I will be presenting some data, some of our experience especially, on the so-called window of opportunity trials, the WOp trials. These are basically the pre-surgical phase II trials with various compounds. We have been actually some of the early pioneers worldwide of this approach which is very intelligent to me because alongside the large cohort, very huge phase III trials which have been absolutely essential to go on with our evidence of the preventive effect of various compounds and drugs, there is also this parallel approach of smaller, sometimes much smaller, phase II trials which have no clinical endpoint, actually, but rather a biological endpoint. They are surrogate endpoint biomarkers trials, basically, and we have been doing a lot of experience on these kinds of trials. We’ve been studying from SERMs like tamoxifen to aromatase inhibitors to TKIs, tyrosine kinase inhibitors, to metformin and also more recently to compounds of natural origin like vegetables, for example green tea derivatives and silybin which is a derivative of an extract of carduus marianus which is a plant. So all these various experiences through the last, approximately, fifteen years have arisen a lot of experience in data on the effect of these drugs. This kind of approach, these clinical research experiments are, from a certain point of view, very difficult to perform because they certainly need a multidisciplinary approach, a very good synchronicity between the clinicians the labs and other data managers and all this stuff. But at the same time, they give the opportunity to study various pharmacological and clinical and biological aspects of the effect of some drugs in a relatively short period of time, most of the time three to six weeks before primary surgery. This may extend to various organs – gynaecological surgery or colorectal cancer, removal of polyps, and breast cancer patients too.
How do you see surrogate endpoint biomarkers being integrated into prevention?
This is one of the most crucial aspects. We must confess we don’t have, at the moment, the perfect biomarkers, of course. Again, one of the endpoints of this study is to try and find more surrogate biomarkers that can be useful for the clinical endpoints, for the clinical application. As a matter of fact, one of the most important and applied is Ki-67, cancer cell proliferation is mostly the one which is used in our pre-surgical studies, at least in breast cancer studies. This one in particular has been proven to be important because if you reduce Ki-67, cancer cell proliferation, before primary surgery this may reflect a long term effect after surgery, in the long term, so in practice a prognostic effect indeed.
How do you see the use of prevention affecting the broader oncology industry?
It is difficult because there are quite a number of barriers against prevention, as said. I think that these rigorous methods of study like the WOp trials or the other trials may reinforce the evidence that clinical prevention, so the clinical approach to prevention, can be ultimately done. So we get more people be more optimistic, more feeling that it can be done ultimately. So I think that this approach from cancer prevention specialists and all the other doctors, all the other colleagues including the GPs, can be increased when you perform all these studies all together and network especially.