Activity of Selumetinib in Pediatric Pilocytic Astrocytoma and Low-Grade Glioma
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.
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/m2twice daily in 28-day courses for up to 26 courses.
Results
Among 25 evaluable patients in stratum 1, 9 (36%) exhibited sustained partial responses; median follow-up among 11 patients who had not had a disease progression event by August 2018 was 36.40 months. Among 25 evaluable patients in stratum 3, 10 (40%) achieved sustained partial responses. Median follow-up among 17 patients without a progression event by August 2018 was 48.60 months.
Among all patients, 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.”
Jason Fangusaro, MD, of Children’s Healthcare of Atlanta and Emory University, is the corresponding author forThe Lancet Oncology article.
Disclosure: The study was funded by the National Cancer Institute Cancer Therapy Evaluation Program, American Lebanese Syrian Associated Charities, and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
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