Dr Francesco Bertolini - European Institute of Oncology, Milan, Italy
Anti-angiogenic therapy as treatment for breast cancer
Tomorrow I will speak about this data set of anti-angiogenic therapy of cancer, particularly of course of breast cancer, because there are two separate fields. At large, in anti-angiogenic therapy for cancer we have some very good results in terms of improved overall survival in a randomised trial involving, for instance, colorectal cancer and lung cancer.
The field of breast cancer is a little bit more controversial in the sense that we have been successful in prolonging the progression free survival so far by adding anti-angiogenic drugs to the conventional chemotherapy, but so far we have not been able to prolong also the overall survival. So clearly there is a lot of room for improvement of this association therapy between chemotherapy and anti-angiogenic therapies. I will talk tomorrow about what are the perspectives for the future improvement of this combination therapy.
Are there any ongoing trials of anti-angiogenic therapy for breast cancer?
Yes, but first of all I would like to discuss what are the pre-clinical basis of these new trials. For instance, we have seen that by adding anti-angiogenic drugs to some kind of so-called metronomic chemotherapy, which is continuous low-dose chemotherapy, there are very interesting results in terms of clinical benefit, which is clinical responses plus stable disease for many, many months. The problem is that sooner or later the patient will relapse and when the patient relapses, the pattern of vascularisation is totally different compared to the pattern of vascularisation which was observed before the combination treatment. So we must understand better at the pre-clinical level, using mice, what are these new patterns of neovascularisation. And we are learning, for instance, that we should add new monoclonal antibodies to the classic anti-VGF monoclonal antibody. For instance, there are antibodies reacting against ALK-1 which is a receptor of the TGF beta broad complex, or antibodies against BV8 which is expressed by some myeloid cells. And this is the pre-clinical basis for future clinical trials of the European Institute of Oncology and in other locations.
Your lab is translational; findings from the mice go through to the clinic?
Exactly. All of the clinical trials that have been done in the field of anti-angiogenic therapy of cancer at the European Institute of Oncology have been in some way led by the pre-clinical observation made in basic research, or in the pre-clinical models of cancer. I do believe that this will be the way we will do also in the near and the next future.
What is the future for this type of therapy?
I do believe that the association therapy and, most of all, the right selection of the patient will be crucial. Of course not all the patients should be treated with the same kind of therapy because that old concept of on average this therapy is good for you will not be working anymore, for economic and biological reasons. So we are working also in the field of trying to define by surrogate biomarkers which are the patients that will take more advantage from this type of therapy. And, for instance, we have published last year and two years ago that selecting at the assessment a particular promising biomarker to select the patients that can benefit from this kind of therapy. This is a surrogate marker of vascular turnover and it seems that patients with a high vascular turnover are the patients that are mostly benefiting from this kind of therapy.