Brain tumors, the first target therapy works
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A targeted therapy, the first, for brain tumors called low-grade gliomas, and capable of reaching exactly where it is needed, overcoming the blood-brain barrier. The new target drug is called vorasidenib and the results of the study that tested it were among the most anticipated at the Asco (American Society of Clinical Oncology) meeting. They were presented in these hours: tested on over 300 patients with slowly progressing gliomas (what doctors call low-grade) it has been shown to be able to increase the time between diagnosis and recovery of the disease by more than double versus placebo: 27.7 months versus 11.1 (median data). “A statistically very strong and very positive figure. This is the first new treatment in 20 years and can finally lead to a change in the prognosis for these neoplasms as well”, he comments. Joseph Lombardineuro-oncologist at the Veneto Oncological Institute (Iov) of Padua, among the 5 Italian centers (together with the Bellaria Hospital of Bologna, the Regina Elena National Cancer Institute of Rome, the Humanitas Clinical Institute of Rozzano and the City of Health and Science of Turin) who took part in the international trial led by the Memorial Sloan Kettering Cancer Center of New York.
SPECIAL ASCO 2023
The mutations and the target drug
The new molecule targets the genetic mutations of two genes, IDH1 and IDH 2, present overall in a very high percentage of patients with these tumors: about 80% for IDH1 and 4-5% for IDH2. “These two genes were identified less than 10 years ago and regulate cell metabolism – explains Lombardi – When they are altered, a ‘wrong’ IDH enzyme is produced which interferes with some mechanisms by promoting cell proliferation. In fact, it increases the synthesis of an onco-metabolite, 2-HG (2-hydroxyglutarate) which promotes tumor growth. The new drug works by blocking the altered IDH enzymes and prevents them from triggering this cascade of events.”
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What are gliomas and how are they classified
Gliomas are quite rare but still the most frequent of the brain tumors. They are distinguished in high-grade gliomas (glioblastoma) which grow faster, and low-grade gliomas (such as astrocytoma and grade 2 oligodendroglioma), which grow much slower but, over the years , also tend to become high-grade and, therefore, more aggressive, transforming, for example, into secondary glioblastomas. Low-grade gliomas mainly affect young adults between the ages of 35 and 40 (2-3 cases per 100,000 inhabitants). This is why after surgery (which is the treatment of choice when it is possible to perform it), depending on the characteristics of the tumor, it is decided to continue with observation alone in cases less at risk of progression, or with chemo-radiotherapy treatments in cases more at risk.
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The vorasidenib study
Over 330 patients (16 to 71 years of age) with non-aggressive low-grade gliomas who had undergone surgery for at least one year (between 1 and 5 years previously) but had not undergone surgery were enrolled in the new international phase III study. undergoing chemo and radiotherapy, and who had residual disease (stable or which had only recently increased in size). The objective of the study was to evaluate whether administering vorasidenib as an alternative to observation alone would prolong the time free from disease progression and, consequently, the time to start of the next treatment with chemo and radiotherapy.
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The results presented at Asco
The participants had been divided into two groups: the first (with 168 patients) took the new target drug, while the second (with 163 patients) a placebo. “Both objectives were achieved: the time from the start of the experimental treatment to progression was more than double in the vorasidenib group compared to placebo. So much so that the observation phase of the study was closed early – underlines Lombardi – Also the start time of a subsequent treatment was longer and the new drug was well tolerated. These data tell us that in patients with low-grade gliomas at a lower risk of progression we can greatly delay the progression of the disease and any side effects of subsequent radio-chemotherapy. It must be said – concludes the expert – that, since IDH is one of the first mutations that occur in these tumors, it is important to intervene early. As the disease progresses, in fact, others are established that maintain the proliferation of the tumor independently of IDH. This study represents a sea change for neuro-oncology, demonstrating that even in a specific subset of brain tumors, targeted therapy can work.”
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