Clinical and NGS predictors of response to regorafenib in recurrent glioblastoma

Clinical and NGS predictors of response to regorafenib in recurrent glioblastoma

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Abstract Predictive factors for response to regorafenib in recurrent glioblastoma, IDH-wildtype, are scarcely recognized.The objective of this study was to identify molecular apunisw2 predictive factors for response to regorafenib using a clinically available platform.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 clinically available platform.Moreover, MGMT methylation and EGFRvIII expression analyses were performed.

Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data.NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases.In the remaining cases, no mutations were detected.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 sophie allport bee curtains months, p = 0.1076).Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (p = 0.

0188).The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases.Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib.We thus provide a molecular selection criterion easy to implement in the clinical practice.