The proneural subtype is not associated with survival benefit from bevacizumab in newly diagnosed glioblastoma: a secondary analysis of the GLARIUS trial

Purpose The AVAglio trial reported a significant survival benefit for first line bevacizumab treatment in patients with IDH wildtype glioblastoma of the proneural gene expression subtype. We here aim to replicate these findings in an independent trial cohort. Methods We evaluate the treatment benefi...

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Published in:Journal of neuro-oncology 2023-09, Vol.164 (3), p.749-755
Main Authors: Weller, Johannes, Zeyen, Thomas, Schäfer, Niklas, Schaub, Christina, Potthoff, Anna-Laura, Steinbach, Joachim P., Hau, Peter, Seidel, Clemens, Goldbrunner, Roland, Tabatabai, Ghazaleh, Vatter, Hartmut, Tzaridis, Theophilos, Schneider, Matthias, Herrlinger, Ulrich
Format: Article
Language:English
Subjects:
Bevacizumab
Brain cancer
Case Study
Gene expression
Glioblastoma
Medicine
Medicine & Public Health
Monoclonal antibodies
Neurology
Oncology
Regression analysis
Survival
Targeted cancer therapy
Tumors
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Summary:Purpose The AVAglio trial reported a significant survival benefit for first line bevacizumab treatment in patients with IDH wildtype glioblastoma of the proneural gene expression subtype. We here aim to replicate these findings in an independent trial cohort. Methods We evaluate the treatment benefit of bevacizumab according to gene expression subtypes of pretreatment tumor samples (n = 123) in the GLARIUS trial (NCT00967330) for MGMT unmethylated glioblastoma patients with Kaplan-Meier analyses, log-rank tests and Cox regression models. Results Employing the Phillips classifier, bevacizumab conferred a significant PFS advantage in patients with proneural IDH wild-type tumors (10.4 vs. 6.0 months, p = 0.002), but no OS advantage (16.4 vs. 17.4 months, p = 0.6). Multivariable analysis adjusting for prognostic covariates confirmed the absence of a significant OS advantage from bevacizumab (hazard ratio, 1.05, 95% CI, 0.42 to 2.64; p = 0.14). Further, there was no interaction between the proneural subtype and treatment arm (p = 0.15). These results were confirmed in analyses of tumor subgroups according to the Verhaak classifier. Conclusion In contrast to AVAglio, glioblastoma gene expression subgroups were not associated with a differential OS benefit from first-line bevacizumab in the GLARIUS trial.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-023-04470-9