Hargrave, Darren R;
Terashima, Keita;
Hara, Junichi;
Kordes, Uwe R;
Upadhyaya, Santhosh A;
Sahm, Felix;
Bouffet, Eric;
... all the Investigators involved in the high-grade glioma cohort; + view all
(2023)
Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600-Mutant Pediatric High-Grade Glioma.
Journal of Clinical Oncology
10.1200/JCO.23.00558.
(In press).
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Abstract
PURPOSE: BRAF V600 mutation is detected in 5%-10% of pediatric high-grade gliomas (pHGGs), and effective treatments are limited. In previous trials, dabrafenib as monotherapy or in combination with trametinib demonstrated activity in children and adults with relapsed/refractory BRAF V600-mutant HGG. METHODS: This phase II study evaluated dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600-mutant pHGG. The primary objective was overall response rate (ORR) by independent review by Response Assessment in Neuro-Oncology criteria. Secondary objectives included ORR by investigator determination, duration of response (DOR), progression-free survival, overall survival (OS), and safety. RESULTS: A total of 41 pediatric patients with previously treated BRAF V600-mutant HGG were enrolled. At primary analysis, median follow-up was 25.1 months, and 51% of patients remained on treatment. Sixteen of 20 discontinuations were due to progressive disease in this relapsed/refractory pHGG population. Independently assessed ORR was 56% (95% CI, 40 to 72). Median DOR was 22.2 months (95% CI, 7.6 months to not reached [NR]). Fourteen deaths were reported. Median OS was 32.8 months (95% CI, 19.2 months to NR). The most common all-cause adverse events (AEs) were pyrexia (51%), headache (34%), and dry skin (32%). Two patients (5%) had AEs (both rash) leading to discontinuation. CONCLUSION: In relapsed/refractory BRAF V600-mutant pHGG, dabrafenib plus trametinib improved ORR versus previous trials of chemotherapy in molecularly unselected patients with pHGG and was associated with durable responses and encouraging survival. These findings suggest that dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAF V600-mutant HGG.
| Type: | Article |
|---|---|
| Title: | Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600-Mutant Pediatric High-Grade Glioma |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1200/JCO.23.00558 |
| Publisher version: | https://doi.org/10.1200/JCO.23.00558 |
| Language: | English |
| Additional information: | This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed. See: https://creativecommons.org/licenses/ |
| Keywords: | All the Investigators involved in the high-grade glioma cohort |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10176306 |
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