468P - Real-world safety of trametinib monotherapy or in combination with dabrafenib in children, adolescents, and young adults with relapsed or refractory low-grade glioma (LGG) and high-grade glioma (HGG)

Background

Trametinib and dabrafenib have shown promising results in LGG and HGG treatment, which are common pediatric tumors. However, their toxicity profile in children has not been fully described.

Methods

The SACHA-France study is a prospective observational study open in all French Society of Pediatric Oncology (SFCE) centers, that collects safety and efficacy data of innovative drugs that are administered to patients ≤ 25 years-old with pediatric malignancies and prescribed either as compassionate or off-label use. All adverse-drug reactions (ADRs) for trametinib in combination with dabrafenib for LGG and HGG with BRAF mutation or trametinib monotherapy for LGG and HGG with BRAF fusion, wildtype LGG and NF1 LGG included in the study from January 2020 to March 2024 are analyzed herein.

Results

In total, 138 patients were included and received trametinib in combination with dabrafenib (cohort A, n=52) or trametinib monotherapy (cohort B, n= 86).

In cohort A, median age was 12.7 years (range: 4.0 – 25.4) and median treatment duration was 24.7 months (range: 1.1 – 48.8). Overall, 32.7% of patients experienced at least one ADR of grade ≥ 2, leading to treatment discontinuation in 3 patients. Six serious ADRs (SADRs) were reported in 3 patients. No grade 5 ADRs were reported. The most common ADRs were skin toxicities (11.5%) and general disorders (13.56%), mainly fever.

In cohort B, median age was 11.3 years (range: 2.1 – 20.6) and median treatment duration was 14.9 months (range: 1.0 – 38.4). Overall, 72.1% of patients presented at least one ADR of grade 2-3, leading to treatment discontinuation in 8 patients. Six SADRs were reported in 4 patients. No grade 4-5 ADRs were reported. The main ADRs were skin (53.5%) and gastrointestinal disorders (11.6%).

Conclusions

To our knowledge, this is the first comprehensive nation-wide study on the safety profile of trametinib and dabrafenib in the pediatric and young adult population. Our data confirm, in the real-life setting, a safety profile similar to that described in previous pediatric studies and in adult patients.

SACHA-France is supported by Imagine for Margo, Association Hubert Gouin, Fondation du LEEM and the SFCE.

Clinical trial identification

NCT04477681.

Editorial acknowledgement

Legal entity responsible for the study

P. Berlanga.

Funding

SACHA-France is supported by Imagine for Margo, Association Hubert Gouin, Fondation du LEEM and the SFCE.

Disclosure

All authors have declared no conflicts of interest.