Details

Autor(en) / Beteiligte

• 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
• Beghella Bartoli, Francesco
• Larocca, Luigi M.
• Lauretti, Liverana
• Olivi, Alessandro
• Pallini, Roberto
• Balducci, Mario
• D’Alessandris, Quintino Giorgio

Titel

Clinical and NGS predictors of response to regorafenib in recurrent glioblastoma

Ist Teil von

• Scientific reports, 2022-09, Vol.12 (1), p.16265-16265, Article 16265

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Abstract Predictive factors for response to regorafenib in recurrent glioblastoma, IDH- wildtype, are scarcely recognized. The objective of this study was to identify molecular 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 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.