Citations 2
BRAF-altered glioma in adults and children: A Society for Neuro-Oncology (SNO) and European Society for Neuro-Oncology (EANO) consensus review on clinical management and future directions
Schreck, Karisa C, Fuente, Macarena I de la, Fat, Mary Jane Lim, Maas, S L, Levy, Jean M Mulcahy, Lombardi, G , Perrault, Sébastien, Petritsch, Claudia , Aldape, Kenneth, Chang, Susan M, Holdhoff, Matthias, Kazda, Tomas, Rhun, Emilie Le, Minniti, Giuseppe, Mueller, Sabine, Preusser, M, Smits, Marion, Weller, Michael, Wen, Patrick Y, Bent, Martin van den, Geurts, Marjolein, Lombardi, Giuseppe , Maas, Sybren L. N. , Schreck, Karisa C. , Levy, Jean M. Mulcahy , Chang, Susan M. , Duerinck, Johnny , Holdhoff, Matthias , Kazda, Tomáš , Rhun, Émilie Le , Minniti, Giuseppe , Mishra, Mark V. , Mueller, Sabine , Padovan, Marta , Preusser, Matthias , Smits, Marion , Weller, Michael , Bent, Martin J. van den , Geurts, Marjolein
Neuro-Oncology | June 5, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Oncogenic BRAF alterations occur in a subset of diffuse gliomas across WHO grades and are increasingly identified through modern molecular diagnostics. In addition to standard glioma therapies, targeted treatments are available for patients with BRAF-altered glioma supported by variable evidence spanning randomized trials, single-arm studies, and real-world evidence. This joint consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO) synthesizes current knowledge on the diagnosis and management of BRAF-altered gliomas across age groups, tumor grades, and lines of therapy. Particular emphasis is placed on expert consensus in clinical scenarios where high-quality trial evidence remains limited. The review addresses rationale testing for BRAF alterations, selection, and monitoring of targeted therapies, management of treatment-related toxicities, approaches to resistance, and priorities for future research. It aims to provide practical, evidence-based guidance for clinicians while highlighting gaps to inform prospective studies.
STELLAR: Phase III, Randomized, Open-Label Study of Eflornithine Plus Lomustine Versus Lomustine Alone in Patients With Recurrent Grade 3 Astrocytoma
Colman, Howard , Lombardi, Giuseppe , Wong, Eric T. , Walbert, Tobias , Lassman, Andrew B. , Peereboom, David M. , Kizilbash, Sani H. , Matsuoka, Carlos Kamiya , Pitz, Marshall , Desjardins, Annick , Kumthekar, Priya , Mason, Warren , Pellerino, Alessia , Butowski, Nicholas , Hamza, Mohamed A. , Lallana, Enrico C., Uhlmann, Erik J. , Welsh, Liam , Wen, Patrick Y. , Dietrich, Jörg , Wang, Chao , Levin, Victor A. , Lassman, Andrew B , Peereboom, David M , Kizilbash, Sani H , Kamiya-Matsuoka, Carlos , Pitz, Marshall W , Strowd, Roy E , Desjardins, Annick , Kumthekar, Priya , Mason, Warren , Pellerino, Alessia , Soffietti, Riccardo , Butowski, Nicholas A , Forsyth, Peter A , Hamza, Mohamed A , Hau, Peter , Nabors, Louis Burt , Uhlmann, Erik J , Welsh, Liam C , Wen, Patrick Yung , Dietrich, Jorg , Wang, Chao , Levin, Victor A , Colman, Howard , Eoli, Marica , Strowd, Roy E. , Soffietti, Riccardo , Hau, Peter , Nabors, Burt , Piccioni, David Eric , Lombardi, G
Journal of Clinical Oncology | December 1, 2025 | Volume: 44 | Issue: 8 | Pages: 641-652
PURPOSE STELLAR (ClinicalTrials.gov identifier: NCT02796261 ) was a phase III, randomized, open-label trial of eflornithine + lomustine versus lomustine monotherapy in patients with recurrent grade 3 astrocytoma. METHODS At trial initiation, eligibility criteria included: age ≥18 years, anaplastic astrocytoma (2016 WHO CNS Tumor classification [WHO CNS4]), first recurrence ≥6 months after radiation and temozolomide (TMZ), Karnofsky performance status ≥70, and no imaging findings consistent with grade 4 glioblastoma. Random assignment (1:1) was stratified by isocitrate dehydrogenase ( IDH ) mutation, age, resection extent, and geography. Patients received eflornithine (2.8 g/m 2 orally, every 8 hours [2 weeks on, 1 week off]) + lomustine (90 mg/m 2 orally, once every 6 weeks), or lomustine monotherapy (110 mg/m 2 once every 6 weeks). The primary end point was overall survival (OS). RESULTS Among 343 patients randomly assigned across 74 sites in eight countries, there was no difference in survival between eflornithine + lomustine and lomustine monotherapy (median OS 23.4 v 20.3 months, hazard ratio [HR], 0.94). Following changes in classification and grading in the 2021 WHO CNS5, a subset analysis of patients with IDH- mutant, grade 3 astrocytoma (n = 196), defined in 2024, before unblinding, showed clinically meaningful improvements in median OS with eflornithine + lomustine versus lomustine monotherapy (34.9 v 23.5 months, HR, 0.64) and median progression-free survival (PFS, 15.8 v 7.2 months, HR, 0.57). No differences were observed among patients with CNS grade 4 disease. Grade ≥3 treatment-emergent adverse events of relevance were related to reversible myelosuppression (eflornithine + lomustine 42% v lomustine monotherapy 29% of patients) and hearing impairment (24% v 0%). No new safety signals were identified. CONCLUSION Clinically meaningful improvements were observed; eflornithine + lomustine doubled PFS and improved OS in patients with recurrent IDH -mutant, grade 3 astrocytoma, but not grade 4 tumors, after prior radiotherapy and TMZ, consistent with its cytostatic mechanism of action.