Journal
CLINICAL CANCER RESEARCH
Volume 25, Issue 24, Pages 7303-7311Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-19-2177
Keywords
-
Categories
Funding
- GlaxoSmithKline
- Novartis
- Novartis Pharmaceuticals Corporation
- NIH/NCI [P30 CA008748]
- NIH Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London
- Women's Auxiliary Millennium Chair in Hematology/Oncology at The Hospital for Sick Children
- Garron Family Chair in Childhood Cancer Research
- National Cancer Institute of the NIH [P50CA165962]
Ask authors/readers for more resources
Purpose: Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor. Patients with BRAF V600 mutation-positive pLGG may benefit from treatment with dabrafenib. Part 2 of a phase I/IIa study, open-label study (NCT01677741) explores the activity and safety of dabrafenib treatment in these patients. Patients and Methods: Patients ages 1 to <18 years who had BRAF V600-mutant solid tumors (>= 1 evaluable lesion) with recurrent, refractory, or progressive disease after >= 1 standard therapy were treated with oral dabrafenib 3.0 to 5.25 mg/kg/day (part 1) or at the recommended phase II dose (RP2D; part 2). Primary objectives were to determine the RP2D (part 1, results presented in a companion paper) and assess clinical activity (part 2). Here, we report the clinical activity, including objective response rates (ORRs) using Response Assessment in Neuro-Oncology criteria and safety across parts 1 and 2. Results: Overall, 32 patients with pLGG were enrolled (part 1, n = 15; part 2, n = 17). Minimum follow-up was 26.2 months. Among all patients, the ORR was 44% [95% confidence interval (CI), 26-62] by independent review. The 1-year progression-free survival rate was 85% (95% CI, 64-94). Treatment-related adverse events (AE) were reported in 29 patients (91%); the most common was fatigue (34%). Grade 3/4 treatment-related AEs were reported in 9 patients (28%). Conclusions: Dabrafenib demonstrated meaningful clinical activity and acceptable tolerability in patients with BRAF V600-mutant pLGG.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available