TY - JOUR
T1 - Efficacy and safety of dabrafenib in pediatric patients with BRAF V600 mutation–positive relapsed or refractory low-grade glioma
T2 - Results from a phase I/IIa study
AU - Hargrave, Darren R.
AU - Bouffet, Eric
AU - Tabori, Uri
AU - Broniscer, Alberto
AU - Cohen, Kenneth J.
AU - Hansford, Jordan R.
AU - Geoerger, Birgit
AU - Hingorani, Pooja
AU - Dunkel, Ira J.
AU - Russo, Mark W.
AU - Tseng, Lillian
AU - Dasgupta, Kohinoor
AU - Gasal, Eduard
AU - Whitlock, James A.
AU - Kieran, Mark W.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/12/15
Y1 - 2019/12/15
N2 - 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 ¼ 15; part 2, n ¼ 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.
AB - 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 ¼ 15; part 2, n ¼ 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.
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U2 - 10.1158/1078-0432.CCR-19-2177
DO - 10.1158/1078-0432.CCR-19-2177
M3 - Article
C2 - 31811016
AN - SCOPUS:85076506426
SN - 1078-0432
VL - 25
SP - 7303
EP - 7311
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -