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Combination of Two FDA Approved Drugs Shows Promise in BRAF V600E‒Mutated Glioma

In short

The results of a phase II trial in patients with BRAF V600E mutations in high- and low-grade glioma, were reported at the 24th meeting of the Society for Neuro-Oncology from November 22 – 24, 2019.

The BRAF inhibitor Tafinlar + the MEK inhibitor Mekinist has demonstrated promising efficacy in recurrent or refractory BRAF V600E-mutated high- and low-grade glioma. Adverse events were manageable and no new safety signals were observed.

Combined BRAF/MEK inhibition also extends the time period until progression and survival in BRAF V600E-mutated melanoma, non-small cell lung cancer (NSCLC), and anaplastic thyroid cancer (ATC).

The study

Eligible patients suffered from histologically confirmed recurrent or progressive glioma (grade 1-4).
Patients with high-grade glioma were required to have received radiotherapy and first-line chemotherapy, or concurrent chemoradiation.

A total of 58 patients were enrolled (n = 45 high-grade glioma; n = 13 low-grade glioma).

Results

  • In patients with high-grade glioma, the disease shrunk or stopped from growing in 29% of patients including complete response in 2 patients, partial response in 11, and stable disease in 12.
  • The disease shrunk or stopped from growing in 29% of Glioblastoma, GBM, patients.
    A total of 68.6% of patients with Glioblastoma, GBM, responded for >12 months.
  • In patients with low-grade glioma, the objective response rate was 62% including 1 complete response, 7 minor or partial responses and stable disease in 2 patients.

Safety

In patients with high-grade glioma, adverse events included fatigue (33%), headache (31%), rash (28%), and pyrexia (23%). Severe adverse events included neutropenia (8%) and fatigue (5%).

In patients with low-grade glioma, adverse events included headache (70%), fatigue (60%), pyrexia (60%), nausea (50%), and arthralgia (50%). Severe adverse events included fatigue (20%).

About Glioblastoma

Glioblastoma Multiforme, or GBM, is a type of cancer which originates in the brain and made of brain cells known as “gliomas.”
Gliomas are neuron supporting cells, constituting a part of the nervous system.
Glioblastoma tends to develop into a star shaped formation. They are particularly aggressive tumors with the potential to grow fast and spread to other parts of the brain relatively quickly.
Glioblastoma creates its own independent blood supply which feeds it, promoting its growth and even enabling it to invade additional areas of the brain and establish more foci, hence the name “multiforme.”
GBM is a stage 4 cancer and constitutes about 50% of all brain tumors among patients aged 18 and older. Glioblastoma does not metastasize outside the brain.

The existing standard therapies used for glioblastoma are not curative, and this is a source of the need for innovative and effective treatment strategies in order to fight the disease.
The National Cancer Institute, NCI, highlights the fact that for a certain group of glioblastoma patients, the best treatment option is to join one of the many clinical trials existing worldwide aiming to increase their chances of therapeutic success.

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Improving therapeutic success, extending life and quality of life are our main business. We extend to metastatic cancer patients and patients with brain tumors, the most advanced treatment options in the world and the best experts in Israel and abroad.

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