BIOM-36. A STUDY OF CLINICAL AND MOLECULAR PROGNOSTIC FACTORS FOR RESPONSE TO REGORAFENIB IN RECURRENT GLIOBLASTOMA. (14th November 2022)

• Record Type: Journal Article
• Authors: Chiesa, Silvia; Mangraviti, Antonella; Martini, Maurizio; Cenci, Tonia; Mazzarella, Ciro; Gaudino, Simona; Bracci, Serena; Martino, Antonella; Della Pepa, Giuseppe M; Offi, Martina; Gessi, Marco; Russo, Rosellina; Martucci, Matia; Bartoli, Francesco Beghella; Bonaventura, Rina Di; Larocca, Luigi M; Lauretti, Liverana; Olivi, Alessandro; Pallini, Roberto; Balducci, Mario; D'Alessandris, Quintino Giorgio
• Is Part Of: Neuro-oncology. Volume 24(2022)Supplement 7
• Page Start: vii12
• Page End: vii12
• Publication Date: 2022-11-14
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac209.046
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Introduction: Following the results from the REGOMA study, regorafenib has become the first chemotherapeutic option for recurrent glioblastoma, IDH- wildtype, in many countries. However, predictive factors for response to regorafenib are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. METHODS: We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH -wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a rapid, cheap, and clinically validated platform. MGMT methylation was assessed using methylation-specific PCR, and EGFRvIII expression was assessed using RT-PCR. RESULTS: In our series, six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months: these data are consistent with current literature. Among clinical variables, gross-total resection was endowed with a positive prognostic value for PFS (p=0.0296, log-rank test). NGS analysis revealed a mutation in the EGFR pathway (EGFR and/or PIK3CA) in 18% of cases; a mutation in the mitogen-activated protein-kinase (MAPK) pathway (RAS and/or RET) in 18% of cases; no mutations in the remaining cases. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p =0.0061; for OS, 7 vs 9 months, p=0.1076). By combining NGS analysis with RT-PCR for EGFRvIII, we identified 14 patients with EGFR pathway activation, who had a significantly longer PFS and OS after regorafenib treatment. Multivariate analysis confirmed that MAPK pathway mutations predicted a scarce response to regorafenib treatment. Conclusions: Through an easy-to-use and cheap platform, we identified a mesenchymal, MAPK-altered signature in IDH-wildtype glioblastoma, predictive of scarce response to regorafenib at recurrence. We thus provide a molecular selection criterion to implement in the clinical practice.