They manage to buy time for the advance of one of the most malignant brain tumors thanks to a new drug

When oncologists explain that while the definitive formula against a tumor arrives, they are only trying to buy time, perhaps what they are trying to do is not appreciated too much.. But if one imagines that we are facing an alarm clock that rings over and over again, and we just want to extend the placid phase of sleep for as long as possible, perhaps we do understand the value of those five minutes more postponed. Those in which, sometimes, it is possible to even dream and we wake up even better.

As long as time cannot be stopped, cancer speeds up the vital counter and the mission of the new drugs is, at least, to slow everything down. “Gaining time is essential,” Juan Manuel Sepúlveda, coordinator of the Neuro-oncology Unit of the 12 de Octubre University Hospital in Madrid, agreed to this outlet..

Simultaneously at the Congress of the American Society of Medical Oncology, which is being held these days in Chicago, and in The New England Journal of Medicine, the impact of an inhibitor called vorasidenib that stops the progression for several years has been announced. a type of malignant brain tumor.

Sepúlveda is the only Spaniard to sign the article, although there has also been participation from other national centers such as the Vall D'Ebron Hospital in Barcelona and the Ramón y Cajal Hospital in Madrid. “We have achieved a new way of approaching grade 2 gliomas with IDH1 and 2 mutations in which tumor signs have been reduced and we see how patients have maintained quality of life over time. It is about delaying relapse for a few years, and with it new chemotherapy sessions and aggressive surgeries”.

This new approach “is going to change clinical practice,” the lead author of the study, Ingo K, said at a press conference.. Mellighoff, of the Department of Neurology at Memorial Sloan Kettering Cancer Center in New York.. In the presentation to the media present at ASCO, he explained that “up to a 61% reduction in the risk of death or progression is achieved and the need to use more toxic therapies in the long term is delayed in a situation of controllable tumor”.

For this reason, “the possible approval of vorasidenib would represent a new targeted therapy for low-grade glioma,” they explain from ASCO.. However, Sepúlveda puts his feet on the ground and, despite the good news that this advance represents for patients, he regrets that it will take time to have an impact outside of trials.. “It has to go to the EMA (European Medicines Agency), after the Aemps (Spanish Agency for Medicines and Health Products) gives it the go-ahead and once approved in Spain that the autonomous communities do not put obstacles and facilitate it. It can take years”.

However, it puts an attractive solution on the table that depends on the laboratory that owns the molecule, Servier Pharmaceuticals.. “I don't know if it could or not, but there is a formula called expanded treatment in which the drug can be administered without being approved under the umbrella of the company, financed by it.. This is just one more idea.”.

What is the profile of the patient who benefits from the new therapy?

The oncologist at the Madrid center draws the profile of the patients who are diagnosed with this malignant tumor, a grade II glioma, who have a high estimated survival time, “between 10 and 20 years.”. These are people in the middle of life, between the ages of 25 and 55, and it occurs in three out of every 100,000 inhabitants per year.. According to the SEOM (Spanish Society of Medical Oncology), primary tumors of the CNS (central nervous system) represent 2% of all cancers in adults..

One of the peculiarities is to identify the IDH1-2 mutation. “This helps us because we have a therapeutic target, a point that helps us release a toxic metabolite that manages to trigger a series of epigenetic damage that damages DNA reading,” says Sepúlveda..

Grade 2 gliomas with a mutation in the IDH gene are malignant brain tumors that cause considerable morbidity and premature death.. These neoplasms grow continuously, albeit slowly, infiltrate the brain and eventually become aggressive tumors with accelerated growth and severe symptoms.. They represent around 30% of brain tumors..

How is the new drug against grade 2 glioma?

It is a drug for oral use, the first inhibitor of the IDH1 and IDH2 mutant enzymes that penetrates the brain. In the trial called Indigo, 331 patients have been included who have been followed for three years. The main conclusion is that in patients with grade 2 IDH mutation glioma, progression-free survival was prolonged by around 30 months compared to placebo administration and the need for treatment was delayed by more than 40 months, being indefinite in some cases. for now.

“The truth is that we have changed their lives; the epileptic seizures that patients suffered as a result of the tumor have decreased, the loss of motor and cognitive functionalities has also decreased, they can return to practicing sports and even in some cases people wear an acceptable life with quality”, emphasizes Sepúlveda.

Vorasidenib, with a low risk of toxicity, produced hardly any notable side effects in the patients undergoing the study. And this is important too. They are people who have undergone surgery, and then it is normal to go on to radiotherapy and chemotherapy. This is the current standard approach, but it is still an aggressive method that leaves traces in the body,” says the Spanish oncologist.

Now, Sepúlveda continues, “we can wait to use chemo or radio. I have patients who have benefited from the drug, first because they had the molecule part of the trial and then we also administered it to those who had a placebo”. This is what the oncologist refers to when he talks about buying time.

On the other hand, the oncologist at the Madrid center also appreciates the collaboration of patients who received placebo for months and still attended tests and medical consultations. “There was a woman who left before finishing because she had postponed her maternity. It was a pity, because we could have offered him the drug. But she is also very grateful because her participation has been important. We immediately realized who had a placebo and who didn't because epileptic seizures were a warning sign.”.

Sepúlveda highlights the case of a patient with a tumor that caused many epileptic seizures and paralysis on the right side. The patient was included in the study and was treated with placebo and after a few months it was seen how the tumor had grown. At that time, treatment with vorasidenib was started and with this, not only was the tumor reduced, but also a significant improvement in its mobility was achieved, as well as complete control of the epileptic seizures.. “We are confident that, with these results, the drug will be available for all patients who have recently undergone surgery for gliomas with this mutation,” he adds..

A mutation found thanks to the atlas of the human genome

When scientists publish a large collection of genome data in the form of an Atlas of the Human Genome and note the theoretical benefits, no one thinks about the impact. “Well, thanks to this advance we have been able to discover the role of IDH and consider its role in the molecular control of cancer”, explains Sepúlveda.