Abstract
Abstract BACKGROUND Pediatric Low-Grade Gliomas (PLGG), encompass a heterogenous set of tumours, with upregulation of RAS/MAPK pathway, making them amenable to therapeutic targeting. MEK inhibitors are emerging as a promising alternative to conventional chemotherapy strategies which have modest efficacy with significant toxicity/hospitalisation and hence long periods of stay away from home (& school). Recently, we transitioned to use of MEK inhibitors, where feasible, in children with PLGG. METHODOLOGY Retrospective analysis of children(<15 years) with newly diagnosed, recurrent/progressive PLGG who received Trametinib at Tata Memorial Hospital, India between September’2021-October’2023. Diagnosis of PLGG was by histopathology/radiology. Molecular testing was performed by qualitative real-time PCR for BRAFV600E and KIAA1549:BRAF fusion. Decision to start MEK inhibitors was taken at the Neuro-oncology MDT meeting. Financial support for therapy was provided through the childhood cancer foundation (ImPaCCT) and other agencies. RESULTS Twenty four children were treated with Trametinib, of which 22 were evaluable for response (>3 months therapy). Median age at start of Trametinib was 6.4 years(2.3–14.5years). Histopathological confirmation of PLGG was done in 19 patients and 5 had a clinico-radiological diagnosis. 13/18(72%) had KIAA1549:BRAF fusion, and 5 were BRAF-Wild type. While 12/22 children received Trametinib as salvage therapy, 10 children received it upfront. 2 received Trametinib due to chemotherapy intolerance. At a median therapy duration of 18 months(3-28 months), 17/22(77%) showed stable disease and 3/22 showed response(2 Partial and 1 minor) as per RANO criteria. Two patients had disease progression [BRAF status included unavailable (n=1), wild-type (n=1)]. Toxicities noted were skin rash(n=8), paronychia(n=3), oral ulcers(n=2) & thrombocytopenia(n=1). Dose reduction due to toxicity was done in one child. School attendance increased and frequency of hospital visits significantly decreased in this cohort. CONCLUSIONS Early experience with Trametinib as an effective/well tolerated alternative to chemotherapy in PLGG is encouraging. Long-term treatment related toxicities and disease control after Trametinib withdrawal are yet unanswered questions.
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