TY  - JOUR
AU  - Fangusaro, Jason
AU  - Onar-Thomas, Arzu
AU  - Young Poussaint, Tina
AU  - Wu, Shengjie
AU  - Ligon, Azra H
AU  - Lindeman, Neal
AU  - Banerjee, Anuradha
AU  - Packer, Roger J
AU  - Kilburn, Lindsay B
AU  - Goldman, Stewart
AU  - Pollack, Ian F
AU  - Qaddoumi, Ibrahim
AU  - Jakacki, Regina I
AU  - Fisher, Paul G
AU  - Dhall, Girish
AU  - Baxter, Patricia
AU  - Kreissman, Susan G
AU  - Stewart, Clinton F
AU  - Jones, David T W
AU  - Pfister, Stefan M
AU  - Vezina, Gilbert
AU  - Stern, Jessica S
AU  - Panigrahy, Ashok
AU  - Patay, Zoltan
AU  - Tamrazi, Benita
AU  - Jones, Jeremy Y
AU  - Haque, Sofia S
AU  - Enterline, David S
AU  - Cha, Soonmee
AU  - Fisher, Michael J
AU  - Doyle, Laurence Austin
AU  - Smith, Malcolm
AU  - Dunkel, Ira J
AU  - Fouladi, Maryam
TI  - Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial.
JO  - The lancet  / Oncology Oncology
VL  - 20
IS  - 7
SN  - 1470-2045
CY  - London
PB  - The Lancet Publ. Group
M1  - DKFZ-2019-01419
SP  - 1011-1022
PY  - 2019
AB  - Paediatric low-grade glioma is the most common CNS tumour of childhood. Although overall survival is good, disease often recurs. No single universally accepted treatment exists for these patients; however, standard cytotoxic chemotherapies are generally used. We aimed to assess the activity of selumetinib, a MEK1/2 inhibitor, in these patients.The Pediatric Brain Tumor Consortium performed a multicentre, phase 2 study in patients with paediatric low-grade glioma in 11 hospitals in the USA. Patients aged 3-21 years with a Lansky or Karnofsky performance score greater than 60 and the presence of recurrent, refractory, or progressive paediatric low-grade glioma after at least one standard therapy were eligible for inclusion. Patients were assigned to six unique strata according to histology, tumour location, NF1 status, and BRAF aberration status; herein, we report the results of strata 1 and 3. Stratum 1 comprised patients with WHO grade I pilocytic astrocytoma harbouring either one of the two most common BRAF aberrations (KIAA1549-BRAF fusion or the BRAFV600E [Val600Glu] mutation). Stratum 3 comprised patients with any neurofibromatosis type 1 (NF1)-associated paediatric low-grade glioma (WHO grades I and II). Selumetinib was provided as capsules given orally at the recommended phase 2 dose of 25 mg/m2 twice daily in 28-day courses for up to 26 courses. The primary endpoint was the proportion of patients with a stratum-specific objective response (partial response or complete response), as assessed by the local site and sustained for at least 8 weeks. All responses were reviewed centrally. All eligible patients who initiated treatment were evaluable for the activity and toxicity analyses. Although the trial is ongoing in other strata, enrolment and planned follow-up is complete for strata 1 and 3. This trial is registered with ClinicalTrials.gov, number NCT01089101.Between July 25, 2013, and June 12, 2015, 25 eligible and evaluable patients were accrued to stratum 1, and between Aug 28, 2013, and June 25, 2015, 25 eligible and evaluable patients were accrued to stratum 3. In stratum 1, nine (36
LB  - PUB:(DE-HGF)16
C6  - pmid:31151904
DO  - DOI:10.1016/S1470-2045(19)30277-3
UR  - https://inrepo02.dkfz.de/record/143857
ER  -