2023-10-04 08:31:40
The renowned specialist calls for promoting the molecular diagnosis of tumors to better identify patients who can benefit from treatments and reduce the toxicity to which the rest are exposed. He directs the Oncology Institute of the Hospital Clínic of Barcelona, in the Faculty of Medicine and is a member of the España Salud Foundation.
The notable advances against cancer achieved by medicine in the last two decades have, for oncologist Aleix Prat (Barcelona, 44 years old), a burden that limits their potential: the limited molecular diagnosis that is made of tumors, something that prevents identifying patients who could benefit most from innovative therapies. “We need to treat 10 patients so that only two or three benefit. The rest pay a high price in toxicity and, furthermore, the economic cost for the system is unsustainable,” summarizes the director of the Clinical Institute of Hematological and Oncological Diseases (ICMHO, in its Catalan acronym).
Recently, the development of a CAR-T therapy against a form of breast cancer, HER2+, has begun. CAR-Ts are innovative treatments that reprogram the patient’s immune system cells to attack cancer cells. The project, in which the 12 de Octubre Hospital in Madrid and the University of Navarra Clinic also participate, is financed with one million euros by El Corte Inglés. The so-called phase I, in which the toxicity and the first data on the efficacy of the therapy are evaluated in a small number of patients, will begin next year.
Ask. Why is molecular diagnosis so important?
Answer. Innovation in new therapies has been enormous in recent years. But at the diagnostic level there has been less progress. We still know little about the biology of tumors and this means that we cannot anticipate in which patients some treatments will be effective. Then we see that there are only a few. As they are expensive drugs, the expense for the health system is enormous and this makes governments think more when financing them. One consequence is that innovation does not reach the patient or takes a long time to reach the patient.
Q. What exactly does molecular diagnosis consist of?
A. Part of the same biopsy that has already been done on the patient to diagnose cancer. But it goes much further when analyzing cancer cells. The genetic material, the chromosomes, the immune system of the tumor are taken… Today we know if a tumor is HER2 [una proteína] positive or negative because it is something that is implemented in clinical practice. But cancer is much more complex. The heterogeneity that exists within HER2 positive people, for example, is enormous. We have to discover these characteristics and give new surnames to each tumor. The well-known Oncotype tests [una prueba que analiza los genes del tejido del cáncer de mama] They already measure several biological processes, but we can take it to a much more complex level.
R. Why isn’t it done if the technology exists that would allow it?
A. It is a complex process. First of all, we are talking about an advanced diagnostic level, with genetic techniques, it is not something that can be done in all hospitals. Second, we need more evidence. What exists tells us that molecular diagnosis can be tremendously useful, but to make therapeutic decisions in each case we need the highest levels of evidence.
Q. And what is missing to have it?
A. There has not been enough investment in transferring all the diagnostic complexity to clinical practice. There are not enough high-level validations, solid clinical trials… Oncotype is once again an example. It was known that it had potential, but until large studies funded by the European Commission or the NCI were carried out [el Instituto Nacional del Cáncer, una agencia pública de Estados Unidos], the level of evidence necessary for it to become a diagnostic routine in hospitals could not be reached. This should be the case with the following biomarkers, which will allow us to know which drugs are effective with each tumor, according to its biology.
Q. That is to say, that governments should invest more.
A. Yes. Governments are interested in studies being carried out that say which treatments should be financed and in which groups of patients. In the medium and long term, bringing molecular diagnosis to clinical routine will bring us closer to a more effective and sustainable system. The European Commission is taking the first steps and has just published the resolution of a call for 40 million euros to finance six clinical trials whose objective is to demonstrate that molecular diagnostic tests improve quality of life and are cost-effective.
Q. And what role does the pharmaceutical industry play?
A. A priori, the industry is not interested in biomarkers. I understand that you do not fund a study that ends up showing that your drugs do not work for a significant portion of patients. Therefore, the role of regulatory agencies is key at this point, because they can require the industry to include molecular diagnosis in its trials.
Q. What are these trials like now?
A. In most cases, clinical studies that can lead to drug approval still do not select patients based on tumor biology; For example, in breast cancer, there are phase III studies that are recruiting thousands of patients and that only take into account whether their tumor is hormonal or not, but nothing else. These trials end up demonstrating a relatively small population benefit. The problem is that sometimes you have to treat, in the most optimal situations, eight or ten patients to benefit one. However, today we have tools that would allow us to divide tumors into subgroups and identify groups of patients that can obtain a relevant clinical benefit. But I think the industry is also changing its position.
R. In what sense?
A. I think it is becoming clear that therapeutic innovation does not reach clinical practice because governments are reluctant to finance therapies with uncertain benefits for many patients. Things would change if the industry could say: ‘Look, three out of four patients improve with this treatment.’ And molecular diagnosis is the way to achieve this. The industry would secure revenue from innovative drugs and governments would get more value for their money. We specialists have to push for the system to advance in this direction and for molecular diagnosis to be put on the same level as therapeutics.
Q. The industry complains a lot that Spain is slow to finance innovation…
A. It is a complex debate. There are drugs that take a long time to reach hospitals and we do not know why, if it is a problem that the price that companies ask for is not related to the therapeutic value, if the Ministry of Health is cautious for budgetary reasons… We do not know what It is what they are discussing and that generates uncertainty and uncomfortable situations. Patients are increasingly informed and see that the drug has been approved by the European Medicines Agency (EMA) and is already used in other countries. So what do you tell them? That there is a treatment available, but that is not paid for? Greater transparency and faster resolution of some special cases would be desirable.
Q. Which ones are you referring to?
A. To those drugs that really provide important value. I am not talking about therapies with a minor or uncertain benefit, but rather others such as immunotherapy in its beginnings or trastuzumab deruxtecan [contra algunos tipos de cáncer de mama], For example. It cannot be that treatments that significantly increase survival spend one or two years in a kind of limbo, without a financing agreement.
Q. Today [por el pasado jueves] have presented the project to develop a CAR-T against breast cancer. The Clínic is a pioneer in this field, with two therapies of this type already developed against acute lymphoblastic leukemia and multiple myeloma. What role will CAR-T developed in public hospitals like the Clínic, called academic hospitals, have in the future?
A. We will undoubtedly have a key role in the future of CAR-T, but I believe it will be complementary to the therapies of this type developed by the pharmaceutical industry. I don’t think we can or should compete, on the contrary. The industry has enormous potential, a capacity that public centers do not reach, and they are subject to very strict regulation at the level of quality, legal, pharmacovigilance… We are at another level and we have to see how it develops from the EMA the regulatory framework so that we can coexist. Oriol Güell (EP)
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