At the end of Pink October, which raises awareness of breast cancer screening, and the entry into Movember, dedicated to male cancers, Professor Pascal Pujol, director of the oncogenetics department of the Montpellier University Hospital, publishes “Exceeding Chemo “. A didactic book which underlines that the treatment, invariably associated with the management of cancer and prescribed to more than 300,000 French people every year, essential in the fight against the disease, is no longer a panacea with the arrival of new therapies.
Professor Pascal Pujol, geneticist, chairs the French society of predictive and personalized medicine.
Do we associate too much “cancer treatment” with chemotherapy, when treatments have evolved?
Exactly. However, the number of chemotherapy is still extremely high. But it is not with chemotherapy that progress has been made in the last 20 years in the treatment of cancer. We have made progress through many other contributions, immunotherapy is one of them, and targeted therapies as well. There are other treatments coming. Progress is not “chemo”, it is not surgery either, and it is not radiotherapy. On the other hand, we do more conservative surgeries, with fewer side effects, and the rays are better dosed. Since the initial successes of chemotherapy in certain cancers, progress has not come from there.
But do we have chemotherapies with fewer side effects over time?
We have not progressed in less toxic “chemos”. On the other hand, much progress has been made in the management of the toxic effects of “chemo”. Me, at the beginning of my career, I told women that they were going to lose their hair and that it was not serious. It’s dramatic to lose hair, it’s an earthquake. We know better how to support women today. I come at length, in the last part of the book, on how to better manage the toxic effects of chemotherapy. There, we made progress.
There are still changes to the process itself…
Yes, there is real progress on so-called targeted chemotherapy, which we call vectorized: your chemo molecule is adapted to specifically recognize the cancerous cell. This is ideal and it works in several cancers. Curiously enough, we have a higher efficiency, but the toxicity is greater, unfortunately. And we can also, in certain cancers, bring chemotherapy to the tumor itself.
“Genomic signatures of tumors help to know if chemo will be useful”
You remember that chemotherapy cures little, less than 10% of cancers, but sometimes it is the lethal weapon.
On leukemia, testicular cancer, yes, and without surgery. it is chemotherapy that cures but it remains very rare, and it is about 10% of cases. One of the most given therapies in France is so-called adjuvant chemotherapy, for breast, lung and colon cancer. We give this because out of 100 people, we know that we will prevent 10 people from reoffending. Only 10% of people will benefit, but we don’t know who. This is why today we are developing so-called genomic signatures of tumours, to know whether chemo will be useful or not.
Can we know this for all chemotherapies?
Unfortunately, today, we only have this information in very few cases, on breast cancer, with a level of proof which makes it possible to avoid 20% or 30% of chemotherapy, it is estimated that 5000 women would be concerned every year.
And we don’t?
The problem is that it is not yet registered in the reimbursement procedures, that it is an obstacle course…. the High Health Authority is in the process of evaluating it and will undoubtedly release something in November, it moves. This is the future of chemotherapy. This process can also be developed for prostate cancer.
Is the “dogma” of chemo, that’s your word, very present in patients, is it also in the medical environment?
Yes, I’ll give you a pretty incredible example. At the world congress which refers, Asco, in June 2022, a communication reported the disappearance of tumors in 16 patients who had advanced, inoperable rectal cancer. In general, they are given chemotherapy, with a 10% to 20% response. There, they were given immunotherapy. In September, the same study was presented on 107 patients, this time there was a 95% complete response. But sorrowful spirits still doubt. On the lung, melanoma, we also have incredible results with targeted therapy in patients who were condemned and who are saved. Today we have to open up to the “challenge”, it’s an Anglo-Saxon word but I can’t find an alternative in French: knowing if when you’re used to doing chemo, you have alternatives for another treatment, often immunotherapy or targeted therapy. This is the next step. We do not yet have this choice: we must compare “chemotherapy + immunotherapy” against “immunotherapy” alone. In oncology, we always pursue the Holy Grail, which is healing. When there is something that works, we do not remove it. Today is the time for the “challenge” trials, these de-escalation trials which make it possible to balance the interest of chemo and another therapy.
“Jimmy Carter was saved by immunotherapy. It’s a miracle”
You cite the incredible story of former US President Jimmy Carter, who was saved by immunotherapy…
He had brain metastases from melanoma, he was 90 years old. In principle, at that age, a priest is called. He was given six months of life. Six years later, he is still there. He was able to benefit from immunotherapy. Today we have success in situations, it was unthinkable! It is on the order of a miracle. And we are only at the beginning.
In new treatments, including immunotherapy and targeted therapy, do we have the key to the management of tomorrow’s cancers?
Most likely. We went around chemo, except for vectorized chemo. You will notice that each year, more than 150,000 people die of cancer in France. If we had the key, it would be known. We must remain modest, be humble. We cannot boast of success when cancer remains the leading cause of death in France. New treatments will be needed. There are already incredible cures with immunotherapy and targeted therapy.
What is the most promising?
There are a multitude of cancers and it is the analysis of the biology of these cancers which will make it possible to personalize the treatment.
There remains the difficulty of innovating…
The 2030 health innovation plan was unveiled this week, the health innovation agency was created, its director was appointed, and the high health authority has just created an evaluation commission… These are promising signals for patients. But there must be fair access to these innovations.