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

• EGFR cancer, the new clue in lung cancer to increase patient survival
• Oncology New therapeutic option prevents relapses in women with the most common breast cancer

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

As long as time cannot be stopped, cancer accelerates the vital counter and the mission of new drugs is at least to make everything go in slow motion. "Gaining time is essential," Juan Manuel Sepúlved, coordinator of the Neuro-oncology Unit at the 12 de Octubre University Hospital in Madrid, agrees to this media.

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 has been announced the impact of an inhibitor called vorasidenib that stops the progression of a type of malignant brain tumor for several years.

Find out more

Bless you.

Foreign Accent Syndrome: When a Brain Injury Steals Part of Your Identity

• Writing: CRISTINA G. LUCIO Madrid
• Writing: EDITING: JOSETXU PIÑEIRO

Foreign Accent Syndrome: When a Brain Injury Steals Part of Your Identity

Research.

Spanish scientists open the door to treating the most lethal pediatric brain tumor with viruses

• Writing: CRISTINA G. LUCIO Madrid

Spanish scientists open the door to treating the most lethal pediatric brain tumor with viruses

Sepúlveda is the only Spaniard who signs 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 in Madrid. "We have achieved a new approach to grade 2 gliomas with IDH1 and 2 mutation in which the signs of the tumor have been reduced and we see how patients have quality of life maintained over time. It's about delaying relapse by a few years, and withit new chemotherapy sessions and aggressive surgeries."

This new approach "is going to change clinical practice," said lead author Ingo K. 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 it achieves "up to a 61% reduction in the risk of death or progression and delays the need to use more toxic therapies in the long term in a controllable tumor situation."

Therefore, "the possible approval of vorasidenib would represent a new targeted therapy for low-grade glioma," ASCO explains. However, Sepúlveda puts his feet on the ground and, despite the good news that this advance represents for patients, regrets that it will take time to have an impact outside the 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 on the table an attractive solution 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, funded by it. This is just one more idea."

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

The oncologist of the Madrid center draws the profile of patients who are diagnosed with this malignant tumor, grade II glioma, who have an estimated high survival time, "between about 10 and 20 years". These are people in the middle of life, between 25 and 55 years and 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 cancer in adults.

One of the particularities 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 damages that damage the reading of DNA, "says Sepúlveda.

Grade 2 gliomas with 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 develop into aggressive tumors with accelerated growth and severe symptoms. They account for around 30% of brain tumours.

What does the new grade 2 glioma drug look like?

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

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

Vorasidenib, with a low risk of toxicity, produced few notable side effects in the patients studied. "And this is important as well. They are people who have undergone surgery, and the normal thing then is to move 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, Sepulveda continues, "we can wait to use chemo or radio. I have patients who have benefited from the drug, first because it touched them in the trial in the part of the molecule and then to those who had placebo we also administered it later." This is what the oncologist means when he talks about buying time.

On the other hand, the oncologist of 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 dropped out before finishing because she had postponed her motherhood. It was a shame, because we could have offered him the drug. But she is equally grateful because her participation has been important. We immediately realized who had 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, which not only shrank the tumor, but also achieved a significant improvement in its mobility, as well as complete control of epileptic seizures. "We are confident that, with these results, the drug will be available to all patients newly operated on for gliomas with this mutation," he says.

A mutation found thanks to the atlas of the human genome

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

• cancer
• Articles Pilar Pérez

According to the criteria of The Trust Project

Learn more