Study: Tafinlar, Mekinist Combination Improves Efficacy in Children With Low-Grade Glioma

Individuals randomized to receive dabrafenib and trametinib had a statistically significant overall response rate of 47% compared with 11% for those who received chemotherapy.

Novartis announced dabrafenib (Tafinlar) and trametinib (Mekinist) significantly improved efficacy in children with BRAF V600 pediatric low-grade glioma, requiring first systemic treatment compared with chemotherapy, which is the standard of care for this patient population.

In the study, individuals who were randomized to receive dabrafenib and trametinib experienced a statistically significant overall response rate (ORR) of 47% compared with 11% for those who received chemotherapy.

Additionally, a new liquid formula of dabrafenib and trametinib was used in this trial and was easier to administer than chemotherapy.

The data were highlighted as a press briefing and oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

“These results show [dabrafenib and trametinib] demonstrate an improvement over chemotherapy for children and adolescents with BRAF V600 low-grade gliomas,” Eric Bouffet, MD, FRCPC, senior associate scientist emeritus at the Hospital for Sick Children in Toronto, Canada, said in a statement. “This work highlights the importance of testing for mutations like BRAF in patients with low-grade gliomas.”

Additional results from the phase 2/3 trial showed that at a median follow-up of 18.9 months, the median progression-free survival was 20.1 months with dabrafenib and trametinib compared with 7.4 months with chemotherapy.

The tumors remained stable or shrank in approximately 86% of individuals receiving dabrafenib and trametinib compared with 46% of individuals in the chemotherapy arm.

After a 1-year follow-up, approximately 89% of the individuals on dabrafenib and trametinib had a reduction in tumor size from the baseline compared with 70% of individuals in the chemotherapy arm.

Investigators reported that the results from a quality-of-life analysis favored dabrafenib and trametinib by comparison with chemotherapy at all time points.

“These young patients and their families experience a heavy burden of care as BRAF V600 low-grade glioma poses a risk of neurological impairment and current standard-of-care treatment is intravenous and associated with frequent trips to the cancer clinic or hospital,” Jeff Legos, executive vice president of Global Head of Oncology & Hematology Development at Novartis, said in the statement. “[Dabrafenib and trametinib] has shown unprecedented efficacy, and we will work with health authorities to bring these children the possibility of a more effective and easier to administer liquid oral treatment option as quickly as possible.”.

Further, the safety profile of dabrafenib and trametinib was generally consistent with the safety profile in previous studies.

Individuals receiving dabrafenib and trametinib had fewer grade 3 or higher adverse events (AEs) and fewer discontinuation because of AEs, at 47% and 4%, respectively, compared with those in the chemotherapy arm, at 94%, and 18%, respectively.

The most common AEs in the dabrafenib and trametinib arm were headaches, pyrexia, and vomiting.

In a separate single-arm cohort of pediatric individuals with refractory or relapsed BRAF V600 high-grade gliomas, treatment with dabrafenib and trametinib showed an independently assessed ORR of 56.1% and had consistent safety results. This cohort’s data were also presented as a poster discussion at the 2022 ASCO Annual Meeting.

The FDA granted dabrafenib and trametinib breakthrough therapy designation for the treatment of pediatric individuals aged 1 year and older with low-grade glioma with a BRAF V600E mutation who require systemic therapy.

Release

Novartis Tafinlar® (dabrafenib) + Mekinist® (trametinib) demonstrates unprecedented efficacy in pediatric patients with BRAF V600 low-grade gliomas in phase II/III study. Novartis. News release. June 6, 2022. Accessed June 7, 2022. Email.