The congress of the European Society of Medical Oncology is being held this year in Paris, from Friday 9 September. On the occasion of this major annual meeting of oncology, its president, the French doctor and researcher Fabrice André, details for L’Express the latest scientific and medical advances against the “crab”, many of which will be the subject of presentations over the weekend. The director of research at Gustave-Roussy relies heavily on advances in biotechnology, which make chemotherapy ever more effective while reducing its side effects, but also on progress in prevention.
L’Express: What is the role of the European Society for Medical Oncology (ESMO, in English), which is holding its annual congress in Paris from September 9 to 13?
Fabrice Andre: ESMO is a learned society, that is to say a non-profit organization which brings together doctors from all over the world, and which aims to disseminate research and good clinical practice. It now has 30,000 members and performs a wide range of activities: issuing certifications, organizing conferences and publishing scientific journals, including Annals of Oncology.
Above all, ESMO partly dictates the scientific agenda. Of course, the political powers play this role in a predominant way. But learned societies, by highlighting certain subjects, allow them to grow and facilitate their development. And therefore indirectly to guide research, since this will attract the interest of researchers, and investments.
Precisely, what are the main topics of the moment?
In the short term, one of the major questions remains the assessment of the impact of targeted therapies and immunotherapy on localized cancers. These treatments, which target the genetic abnormalities of tumors for the first, and which consist in lifting the brakes of the immune system for the second, were first administered to patients with metastatic diseases. They have already demonstrated great efficacy in this population, even if the proportion of responder patients remains low. For about two years, they have been tested in patients suffering from less advanced cancers. We hope that they will prove even more effective, because these tumours, which are often less complex, contain fewer genetic abnormalities. There is therefore less risk of seeing resistance to treatment appear. Several presentations will be devoted to this theme at ESMO, even if it is not the newest.
“Thanks to biotechnologies, we are building new, more targeted therapies”
What questions have emerged more recently?
Everything related to biotechnology, thanks to which we build new, more targeted therapies. In particular conjugated antibodies, which combine a monoclonal antibody and chemotherapy. They bring the toxic molecule directly into tumor cells, sparing healthy cells. This allows for the use of more potent drugs, which we would otherwise not administer because of their side effects. For now, they are given only in patients with metastatic disease, but they are proving to be very effective and will probably eventually replace chemotherapy as we know it today. We also have more and more bispecific antibodies which, by targeting two targets on the surface of cancerous cells, also make it possible to limit adverse effects. Finally, we are seeing the emergence of cellular therapies, with “car-t” cells or TILs, which are two families of T lymphocytes modified in the laboratory to attack cancer cells.
These are important subjects: part of the investments in cancer research, traditionally devoted to understanding the mechanisms of the disease, are redirected towards therapeutic biotechnologies, and also diagnostics.
What are diagnostic biotechnologies?
The more we widen the range of treatments, the more they become personalized, and the more we need tests to predict the effectiveness of such and such a drug in a patient. High-throughput sequencing of tumors has contributed a great deal to knowledge of their genetic characteristics, and therefore of the usefulness of products targeting one mutation rather than another. Today, research focuses on organoid technologies: it involves reproducing living cancer outside the patient, in the laboratory. From there, we can genetically manipulate it, expose it to drugs, to understand how it reacts. Many clinical trials are underway, including at Gustave-Roussy.
“AI and digital technology will make it possible to standardize the quality of care”
What avenues will be discussed for the future?
First, artificial intelligence (AI). As in all emerging fields, we see a bit of everything at the moment, when in reality, the teams that create really promising tools remain few in number. But interesting applications are nevertheless appearing, for making diagnoses, predicting survival times or the effectiveness of drugs. All at low cost and with limited human intervention. This seems to me to be a way forward, in particular to reduce inequalities in access to care.
Ditto for the digital put at the service of the follow-up of the patients. We had seen the beginnings of this a few years ago with lung cancer. At present, large companies are conducting phase 3 studies and are able to show effectiveness in identifying relapsed patients very early on, and better taking care of them. These solutions will make it possible to standardize the quality of care, but also to reduce the tensions on the nursing staff, while making their job more attractive.
What about prevention?
This is an essential subject, which we will be highlighting extensively at ESMO. With in particular research aimed at detecting tumors ever earlier. We talk about it because now there are tests available. They are based on the search for tumor DNA circulating in the blood of individuals. The idea would then be to take a simple blood test every six months or every year to monitor the appearance of tumors and treat them at a very early stage. The United States markets a test that can identify 30% of pancreatic cancers, for example, with some false positives…
And above all 70% false negatives: isn’t there a risk of wrongly reassuring too many patients?
We don’t reason like that… By detecting 30% of cancers early instead of zero, cancer mortality will inevitably decrease. The challenge of these tests is to know how they will be distributed. Of course, they will not be marketed larga manu – even if they are in the United States. We have to think about who to offer them to, and above all how to support patients according to the result. Because even if it is negative, that does not mean that you have to give up other screening programs, quite the contrary. This is why they will necessarily have to be made available under the supervision of doctors. We will be discussing these topics at ESMO, as well as the tests currently in development.
“We can demonstrate the existence of causal links between certain pollutants and the appearance of tumours”
Is pancreatic cancer the only one affected?
No, but it is important for this disease, which is often diagnosed at too late stages today. Cancers linked to the HPV virus (cancers of the cervix, in particular, editor’s note) can also be detected very early on by tests. It works poorly for breast cancer, but I’m not sure we need it because the issues that remain unresolved today are primarily therapeutic issues. They concern breast cancer subtypes, such as very aggressive so-called “triple negative” cancers, for which it is possible that some of these tumors appear too quickly to be detected early.
In terms of prevention, we will also have presentations on the role of pollution in the appearance of cancer. Because today, molecular epidemiology makes it possible to link exposures to the molecular subtypes of cancers. This makes it possible to identify mechanisms and therefore to demonstrate a causal link between an exposure and a tumour.
With all these innovations, can we hope to see a further increase in recovery rates, or are we rather taking measures that make it possible to prolong the lives of patients?
Both. In metastatic cancers, apart from those that are very responsive to immunotherapy where we can truly speak of a cure, it is always a question of prolonging the life of patients. They are in fact very often characterized by the appearance of resistance which we deal with before reaching the end of our therapeutic arsenal. On the other hand, in localized cancers, the cure rates are increased, with patients who no longer relapse. By definition, we will then have fewer metastatic diseases, since the patients concerned are often those who relapse. With the combination of all these measures, therapeutic advances, early detection and prevention, we are bound to continue to reduce cancer mortality in the years to come.
Is cancer treatment affected by the difficulties of recruiting healthcare personnel, which we encounter in France but also throughout Europe?
Yes, but advances in research may also provide answers to this question. This is the whole subject of the ‘de-escalation’ of care: could we not replace complex, long, often toxic protocols with shorter-term treatments which also have less impact on the quality of life of sick? This question is very much related to the way clinical trials are carried out. To show the benefit of this or that molecule, we give as much as possible. This is normal, but in reality it is very likely that at least some of the patients do not need as much treatment. So other tests must follow, to show the minimum quantity to be administered. With the scarcity of caregivers, this subject becomes even more important. This is why we have also chosen to highlight in the plenary session a study which shows that a few weeks of immunotherapy are enough to cure a subtype of colon cancer. There is no need to do several months of additional chemotherapy. This is a small study, but ESMO experts considered it to be a significant step forward.