In a nonrandomised, open-label phase 2 study, MD Anderson researchers showed that the combination of BRAF inhibitor dabrafenib and MEK inhibitor trametinib had promising efficacy in patients with BRAF V600 mutation-positive HGG and LGG.
BRAF mutations occur in approximately 3% of glioblastomas and 15% of low-grade gliomas.
The FDA approved a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib, which blocks proteins that facilitate cancer cell growth, to treat patients with BRAF V600-positive melanoma, non-small cell lung carcinoma and anaplastic thyroid cancer.
"Glioblastoma is a very difficult-to-treat tumour and has historically shown resistance to therapies, and this is the first time that a targeted therapy has shown significant activity in these challenging tumours," said Subbiah, who presented these findings at the virtual AACR Annual Meeting 2021.
The HGG arm of the trial enrolled 45 patients previously treated with radiotherapy, surgery or chemotherapy.
A majority of patients had glioblastoma, while the rest had anaplastic pleomorphic xanthoastrocytoma and anaplastic astrocytoma.
After undergoing the combination therapy, patients showed a 33% objective response rate.
The tumours continued to respond to treatment without cancer growth or spread for 36.9 months.
While 13 patients were enrolled in the LGG cohort, eight patients -- who were previously treated with surgery, radiotherapy and chemotherapy -- were evaluated in the study and achieved an objective response rate of 69%.
The median duration of response, median progression-free survival and median overall survival rates were not reached.
Among both cohorts, 54 patients (93%) experienced a common adverse event -- including fatigue, headache, nausea and fever -- and 31 patients (53%) experienced a Grade 3 or greater adverse event -- such as fatigue, decreased neutrophil count, headache and neutropenia.
No new safety signals were detected.
Ultimately, results from this basket trial show that dabrafenib combined with trametinib achieved meaningful response rates in patients with recurrent gliomas with BRAF V600E mutations, regardless of glioma subtype.
"Molecular screening strategies that include BRAF V600E mutations will be crucial for identifying patients who may benefit from these therapies," Subbiah said. "We recommend that testing is adopted in clinical practice for patients with glioma."