Molecular Correlates of Long-Term Response to Bevacizumab in Glioblastoma

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PURPOSE The use of bevacizumab in glioblastoma has been associated with increased progression-free survival and improvement in symptoms and quality of life. There are no clinical indicators on how to choose patients who would benefit the most from this agent. We aim to describe molecular markers in patients with glioblastoma who may benefit from treatment. Methods We analyzed glioblastoma tumor samples that underwent comprehensive molecular profiling analysis at Caris Life Sciences. RESULTS The data set consisted of 3,106 glioblastoma tumor samples, of which 571 were from patients treated with bevacizumab. The majority were males (65%) and older than 60 years. Median survival was 17.5 months in patients receiving bevacizumab. In patients who were treated with bevacizumab for ≥1 year, median survival was 33.8 months, compared with 15 months in those treated for ≤6 months. Patients who received bevacizumab for ≥1 year had higher prevalence of LRIG3 (9% v 1%), CDK4 (22% v 8%), and DDIT3 amplification (14% v 4%), SETD2 mutations (10% v 3%), and MGMT methylation (66% v 32%). EGFR amplification was more frequent in patients who received bevacizumab for ≤6 months (46% v 20%). Multivariate analysis showed that CDK4 amplification was associated with longer time on bevacizumab, and EGFR amplification with shorter time after correcting for age, sex, and other molecular alterations. CONCLUSION CDK4 amplification is a potential genetic biomarker to identify patients who may derive prolonged benefit from bevacizumab.

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