Jason Fangusaro, MD
In a phase II trial reported in The Lancet Oncology, Jason Fangusaro, MD, and colleagues 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.
The current 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 (KIAA1549–BRAF fusion or the BRAF V600E [Val600Glu] mutation). Stratum 3 included patients with any NF1-associated pediatric grade I or II glioma.
Patients received oral selumetinib at 25 mg/m2 twice daily in 28-day courses for up to 26 courses.
Among 25 evaluable patients in stratum 1, 9 (36%) exhibited sustained partial responses. The median follow-up among 11 patients who had not experienced a disease progression event by August 2018 was 36.40 months. Among 25 evaluable patients in stratum 3, 10 (40%) achieved sustained partial responses. The median follow-up among 17 patients without a disease progression event by August 2018 was 48.60 months.
Among all patients in the trial, the most common grade ≥ 3 adverse events were elevated creatine phosphokinase (10%) and maculopapular rash (10%). No treatment-related deaths occurred.
The investigators concluded, “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.” ■