Efficacy of Dabrafenib for three children with brainstem BRAF V600E positive ganglioglioma

Purpose Children with unresectable brainstem-infiltrated ganglioglioma have poor progression-free survival when treated with conventional chemotherapy and radiation regimens. The BRAF V600E mutation occurs in a large number of gangliogliomas, making them amenable for targeted therapy using mutation-specific kinase inhibitors. However, limited data exists on the effectiveness and best treatment duration of these inhibitors in this tumor setting. Method Retrospective description of three cases of childhood brainstem ganglioglioma with BRAF V600E mutation treated in the long-term with Dabrafenib, a specific BRAF V600E kinase inhibitor. Results Dabrafenib resulted in rapid tumoral regression and significant and durable clinical and radiological improvement. However, all patients had rapid clinical and radiological relapse within days to weeks following treatment discontinuation but showed similar rapid and sustained therapeutic response when Dabrafenib was re-introduced. This targeted therapy has been well tolerated despite its long-term use of 4.8 to 5.5 years in the three patients. Conclusion Dabrafenib is effective and seemingly safe and well tolerated in our three patients. We observed sustained chemosensitivity even when re-introducing this kinase inhibitor after its discontinuation after 2 years of therapy. These cases indicate the need to re-evaluate the timing and means of Dabrafenib discontinuation in pediatric patients with BRAF V600E mutated gangliogliomas and better assess the future implications of its long-term use.