Combination dabrafenib and trametinib demonstrated antitumor activity in patients with recurrent high-grade or low-grade glioma with BRAF V600E mutations, according to research published in The Lancet Oncology.

Researchers are evaluating dabrafenib plus trametinib in patients with a variety of BRAF V600E mutation-positive cancers as part of the ongoing phase 2 ROAR trial (ClinicalTrials.gov Identifier: NCT02034110).

The current results include only patients with recurrent glioma — 45 with high-grade glioma and 13 with low-grade glioma. In the high-grade cohort, the median age was 42 years (range, 18-72 years), and 51% were men. In the low-grade cohort, the median age was 33 years (range, 18-58 years), and 69% were women.


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All patients received oral dabrafenib (150 mg twice daily) and oral trametinib (2 mg once daily) until unacceptable toxicity, disease progression, or death.

In the high-grade glioma cohort, the median follow-up was 12.7 months. By investigator assessment, the objective response rate was 33% (15/45). There were 3 complete responses and 12 partial responses.

In the low-grade glioma cohort, the median follow-up was 32.2 months. The objective response rate was 69% (9/13). One patient had a complete response, 6 had partial responses, and 2 had minor responses.

Adverse events (AEs) were reported in 93% of patients (54/58), 47% in the high-grade glioma cohort and 61% in the low-grade cohort.

Grade 3 or higher adverse events occurred in 53% of patients, the most common being fatigue (9%), decreased neutrophil count (9%), headache (5%), and neutropenia (5%).

Based on these findings, the researchers suggested that dabrafenib plus trametinib is a promising treatment option for patients with BRAF V600E-mutant, recurrent high-grade or low-grade glioma.

The team recommended routine testing for BRAF V600E mutations in clinical practice to identify patients who might benefit from this combination.

Disclosures: This research was supported by Novartis Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Wen PY, Stein A, van den Bent M, et al. Dabrafenib plus trametinib in patients with BRAF V600E-mutant low-grade and high-grade glioma (ROAR): A multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol. Published online November 24, 2021. doi:10.1016/S1470-2045(21)00578-7