Science

Cancer, new leads: “We will have fewer patients with metastases in the future”

The Congress of the European Society for Medical Oncology takes place this year in Paris from Friday 9 September. On the occasion of this major annual oncology gathering, its president, French physician and researcher Fabrice André, detailed the latest scientific and medical advances in the fight against “crabs” to L’Express, 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 are making chemotherapy even more effective while reducing its side effects, as well as advances in prevention.

L’Express: What is the role of the European Society for Medical Oncology (ESMO, in English), which holds its annual congress in Paris from 9 to 13 September?

Fabrice André: ESMO is a scientific society, that is, a non-profit organization that brings together physicians from all over the world and seeks to disseminate research results and clinical excellence. It currently has 30,000 members and carries out a wide range of activities: it issues certificates, organizes conferences and publishes scientific journals, including the Annals of Oncology.

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First of all, ESMO partly dictates the scientific agenda. Of course, this role is mainly played by political forces. But learned societies, by highlighting certain subjects, allow them to grow and contribute to their development. And therefore direct research indirectly, as this will attract the interest of researchers and investments.

What are the main themes at the moment?

In the short term, assessing the impact of targeted therapies and immunotherapy on localized cancers remains a major issue. These therapies, which target the genetic abnormalities of the tumors for the former and release the brakes on the immune system for the latter, were first applied to patients with metastatic disease. They have already demonstrated high efficacy in this population, even if response rates remain low. For about two years, they were tested on patients suffering from less common cancer. We hope that they will be even more effective, because these tumors, often less complex, contain fewer genetic abnormalities. Therefore, there is a lower risk of developing resistance to treatment. Several reports will be devoted to this topic at ESMO, even if it is not the newest one.

“Thanks to biotechnology, we are creating new, more targeted treatments”

What questions have come up recently?

Everything related to biotechnology, thanks to which we create new, more targeted treatments. In particular, conjugated antibodies that combine a monoclonal antibody and chemotherapy. They deliver the toxic molecule directly to tumor cells while sparing healthy cells. This allows us to use more powerful drugs that we would not otherwise use because of their side effects. For now, they are only given to patients with metastatic disease, but they have proven to be very effective and will likely eventually replace chemotherapy as we know it today. We also have more and more bispecific antibodies that, by acting on two targets on the surface of cancer cells, also help limit side effects. Finally, we are seeing the emergence of cell therapy with “car-t” cells, or TILs, which are two families of T lymphocytes that have been modified in the laboratory to attack cancer cells.

These are important topics: part of the investment in cancer research, traditionally aimed at understanding the mechanisms of the disease, is being redirected towards therapeutic biotechnologies, as well as diagnostics.

What is diagnostic biotechnology?

The more we expand the spectrum of treatment, the more it becomes personalized, and the more we need tests to predict the effectiveness of a given drug in a patient. High-throughput sequencing of tumors has greatly contributed to the understanding of their genetic characteristics and thus the utility of products that target one mutation rather than another. Today, research is focused on organoid technologies: we are talking about reproducing live cancer outside the patient, in the laboratory. From there, we can genetically manipulate him, drug him, to understand how he reacts. Many clinical trials are underway, including in Gustave-Roussy.

“Artificial intelligence and digital technologies will standardize the quality of medical care”

What directions will be discussed for the future?

First, artificial intelligence (AI). As in all new areas, we see a little bit of everything at a time when in reality there are few teams that create really promising tools. But nevertheless, there are interesting applications for making diagnoses, predicting the survival time or the effectiveness of drugs. All at a low cost and with limited human intervention. It seems to me that this is the way forward, in particular, reducing disparities in access to health care.

The same goes for digital technologies designed to monitor patients. We saw the beginning of this a few years ago with lung cancer. Large companies are currently conducting Phase 3 trials and may show effectiveness in identifying patients with relapses at a very early stage and improving their care. These solutions will standardize the quality of care, as well as reduce the burden on medical staff, making their work more attractive.

How about prevention?

This is an important topic that we will cover extensively at ESMO. In particular, research aimed at detecting tumors as early as possible. We are talking about this because there are now tests available. They are based on the search for tumor DNA circulating in the blood of individuals. The idea would be to have a simple blood test every six months or every year to monitor for tumors and treat them at a very early stage. A test is sold in the United States that can detect 30% of pancreatic cancers, for example, with some false positives…

And, above all, the 70% false-negative results: is there a risk of erroneously reassuring too many patients?

We don’t think like that… With early detection of 30% of cancer cases instead of zero, cancer mortality will inevitably decrease. The purpose of these tests is to find out how they will be distributed. Of course, they won’t be sold to the larga manu, even if they are in the United States. We must think about who to offer them to, and above all, how to support patients in accordance with the result. Because even if it is negative, it does not mean that you should refuse other screening programs, quite the contrary. Therefore, they must be available under the supervision of doctors. We will be discussing these topics at ESMO as well as tests currently in development.

“We can demonstrate a causal relationship between some pollutants and the appearance of tumors”

Only pancreatic cancer strikes?

No, but it is important in this disease, which today is often diagnosed too late. Cancers associated with the HPV virus (particularly cervical cancer, editor’s note) can also be detected at a very early stage with tests. It doesn’t work well for breast cancer, but I’m not sure we need it because the problems that remain unresolved today are mostly therapeutic. They concern subtypes of breast cancer, such as the very aggressive so-called “triple negative” cancers, for which it is possible that some of these tumors appear too quickly to be detected at an early stage.

In terms of prevention, we will also have presentations on the role of pollution in causing cancer. Because today molecular epidemiology makes it possible to link exposures to molecular subtypes of cancer. This allows mechanisms to be identified and therefore a causal relationship between radiation exposure and tumor to be demonstrated.

With all these innovations, is it possible to hope for a further increase in recovery rates, or are we rather taking measures to prolong the life of patients?

Both. With metastatic cancer, except for those that respond very well to immunotherapy, where we can really talk about a cure, it is always about prolonging the life of patients. In fact, they are very often characterized by the emergence of resistance, which we deal with before we exhaust our therapeutic arsenal. On the other hand, with localized cancer, cure rates increase and patients no longer recur. By definition, then we will have fewer metastatic diseases, since we are talking about patients who often relapse. By combining all these measures, therapeutic advances, early detection and prevention, we are sure to continue to reduce cancer deaths in the coming years.

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Are cancer treatments affected by the recruitment difficulties we face in France and across Europe?

Yes, but advances in research may also provide answers to this question. This is the whole point of the “de-escalation” of care: is it possible to replace complex, long, often toxic protocols with shorter-term treatments, which, moreover, have less impact on the quality of life of patients? This question has a lot to do with how clinical trials are conducted. To show the benefit of this or that molecule, we give as much as possible. This is normal, but in fact it is very likely that at least some patients do not need such treatment. So other tests must follow to show the minimum amount that needs to be entered. In the context of a shortage of caregivers, this issue becomes even more important. That’s why we also decided to highlight in plenary a study that shows that a few weeks of immunotherapy is 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 considered it a significant step forward.

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