Dabrafenib-trametinib combo improves response in BRAF V600-mutant paediatric glioma

First-line treatment with dabrafenib plus trametinib significantly increased overall response rate (ORR) in paediatric patients with low-grade glioma harbouring BRAF V600 mutations compared with standard chemotherapy, according to a recent study.

At a median follow-up of 18.9 months, as assessed by an independent review committee per RANO* criteria, a significantly higher ORR (complete or partial response) was observed among patients treated with dabrafenib plus trametinib compared with chemotherapy (47 percent vs 11 percent; risk ratio [RR], 4.31; p<0.001). [N Engl J Med 2023;389:1108-1120]

“In addition, responses were observed across the diverse histologic types of glioma in this trial, findings that support broad use of dabrafenib plus trametinib as first-line therapy in this population,” the researchers noted.

This phase II trial analysed 110 patients (aged 1–17 years) with low-grade glioma with BRAF V600 mutations who were randomized to receive either oral dabrafenib* divided into two equal doses per day and trametinib** once daily (n=73) or standard chemotherapy (n=37).

Patients treated with dabrafenib plus trametinib achieved a significantly longer progression-free survival (PFS) compared with chemotherapy (median 20.1 vs 7.4 months; hazard ratio, 0.31; p<0.001).

The 6-month PFS rate was higher in the dabrafenib plus trametinib vs the chemotherapy arm (87 percent vs 58 percent), and this PFS advantage was sustained through 12 months (67 percent vs 26 percent).

More dabrafenib plus trametinib recipients also experienced a clinical benefit, defined as complete or partial response or stable disease for ≥24 weeks, than chemotherapy recipients (86 percent vs 46 percent; RR, 1.88).

“The clinical benefit of dabrafenib plus trametinib as compared with chemotherapy is further supported by greater improvements in visual acuity and global health,” noted the researchers.

In terms of safety, grade ≥3 adverse events (AEs) occurred at a lower rate in the dabrafenib plus trametinib arm vs the chemotherapy arm (47 percent vs 94 percent), with no deaths reported in the dabrafenib plus trametinib arm.

“Overall, this randomized trial shows the superiority of dabrafenib plus trametinib as first systemic therapy for paediatric patients with low-grade glioma with BRAF V600 mutations as compared with carboplatin plus vincristine, the standard chemotherapy approach,” said the researchers.