Cancer Treatment Today

The U.S. Food and Drug Administration approved Koselugo (selumetinib) for the treatment of pediatric patients, 2 years of age and older, with neurofibromatosis type 1 (NF1), a genetic disorder of the nervous system causing tumors to grow on nerves. It is not approved for this patient’s cancer type.

In a phase II trial reported in The Lancet Oncology, Fangusaro et al found that the MEK1/2 inhibitor selumetinib was active in pediatric patients with recurrent, refractory, or progressive pilocytic astrocytoma with common BRAF aberrations and neurofibromatosis type 1 (NF1)-associated low-grade glioma.

Another report from The Pediatric Brain Tumor Consortium trial, conducted at 11 U.S. sites, provides findings in two of six patient strata. Stratum 1 included patients with World Health Organization grade I pilocytic astrocytoma with either of the two most common BRAF aberrations (KIAA1549BRAF fusion or the BRAF V600E [Val600Glu] mutation). Stratum 3 included patients with any NF1-associated pediatric grade I or II glioma.

Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma. These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children’s Oncology Group phase III studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed, pediatric low-grade glioma both with and without NF1.
J. Fangusaro et al, Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet, VOLUME 20, ISSUE 7, P1011-1022, JULY 01, 2019

A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study.
Neuro Oncol. 2017; 19: 1135-1144