ID #98 A Phase 2 Re-treatment Study of Selumetinib for Recurrent/Progressive Pediatric Low-Grade Glioma (pLGG): A Pediatric Brain Tumor Consortium (PBTC) Study, PBTC-029C
Jason Fangusaro, Arzu Onar-Thomas, Shengjie Wu, Shelly Lensing, Roger Packer, Lindsay Kilburn, Ibrahim Qaddoumi, Girish Dhall, Ian Pollack, Alicia Lenzen, Sonia Partap, Tina Poussaint, Maryam Fouladi, Ira DunkelAbstract
Introduction
The PBTC conducted a re-treatment study evaluating selumetinib, a MEK I/II inhibitor, in children with recurrent/progressive pLGG. Eligible patients were previously enrolled on the phase 1/2 PBTC-029 trial, had stable disease (SD) for a minimum of 12 courses or had response during initial selumetinib exposure, and then progressed after coming off selumetinib.
Methods
Dual primary endpoints were objective response and 12-month disease stabilization. The secondary endpoint was PFS. The design followed a bivariate binomial two-stage approach.
Results
Thirty-five patients who progressed at a median of 7.3 months (0.3-40.8) post-initial therapy were enrolled. 19/35 (54%) had optic pathway/hypothalamic location, and 21/35 (60%) had pilocytic astrocytoma histology. Success criteria were > 7 objective responses or > 23 patients with SD after 12 cycles. The overall response rate was 5/35 (14.3%), 4 within 12 courses, all partial responses. Thirty patients (86%) had stable disease for ≥ 12 cycles. Median treatment duration was 27.6 months (1.9-86.9), and median response duration was 22.4 months (5.8-65.6). The 1-year/5-year PFS were 88.6%/55.6%, respectively. There was no association between re-treatment PFS to BRAF aberration, initial response to re-treatment response, or initial PFS to re-treatment PFS. 17/35 (49%) patients progressed, 9 on re-treatment and 8 after stopping re-treatment. The most common attributable toxicities were grade 1 and similar to initial treatment. The most common grade 3/4 toxicity was elevated CPK among 5/35 (14.2%) patients. There were no notable differences in toxicities between initial therapy and re-treatment.
Conclusion
Per the statistical design, re-treatment with selumetinib was effective in pLGG patients who had recurred/progressed after stopping initial treatment with selumetinib. The observed benefit was primarily in prolongation of PFS with 86% of patients being progression-free at 1-year, and over 50% being progression free at 5 years. Selumetinib re-treatment should be considered in patients who benefited from initial treatment.