An ANOCEF Genomic and Transcriptomic Microarray Study of the Response to Irinotecan and Bevacizumab in Recurrent Glioblastomas

Abstract

Background. We performed a retrospective study to assess whether the initial molecular characteristics of glioblastomas (GBMs) were associated with the response to the bevacizumab/irinotecan chemotherapy regimen given at recurrence. Results. Comparison of the genomic and gene expression profiles of the responders (n = 12) and nonresponders (n = 13) demonstrated only slight differences and could not identify any robust biomarkers associated with the response. In contrast, a significant association was observed between GBMs molecular subtypes and response rates. GBMs assigned to molecular subtype IGS-18 and to classical subtype had a lower response rate than those assigned to other subtypes. In an independent series of 33 patients, neither EGFR amplification nor CDKN2A deletion (which are frequent in IGS-18 and classical GBMs) was significantly associated with the response rate, suggesting that these two alterations are unlikely to explain the lower response rate of these GBMs molecular subtypes. Conclusion. Despite its limited sample size, the present study suggests that comparing the initial molecular profiles of responders and nonresponders might not be an effective strategy to identify biomarkers of the response to bevacizumab given at recurrence. Yet it suggests that the response rate might differ among GBMs molecular subtypes.

Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

“…In line with others [12], we found no significant differences between pretreatment samples of responders and non-responders. Considering the extreme inter-tumor heterogeneity of glioblastoma and the small sample size, this was not unexpected.…”

“…Nevertheless, gene expression profiling of glioblastoma has identified four molecular subtypes, namely Neural, Proneural, Classical and Mesenchymal, and preliminary evidence indicates survival benefit in distinct molecular subtypes treated with bevacizumab combination therapy [10, 11]. However, the results of these two studies have been inconsistent and we have along with others shown that the subtypes do not impact bevacizumab response in recurrent glioblastoma [12, 13]. …”

Identification of transcriptome signature for predicting clinical response to bevacizumab in recurrent glioblastoma

“…Genomic profiling of corresponding tumors did not demonstrate any significant difference between responders and nonresponders in terms of core oncogenic pathways that are frequently altered in GBM. However, transcriptome analysis showed a difference in terms of molecular subtype consistent with previous studies , majority of the nonresponders were classified as classical subtype, while responder cases were mainly comprised of the nonclassical subtype. Notably, two large independent clinical trials have reported the predictive role of transcriptional molecular subtype in clinical response .…”

Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial

“…Based on data provided in this article, it would be interesting to see whether in those studies tumors assigned to IGS-18 also show benefit from the addition of bevacizumab to chemotherapy. Of note, in a recent retrospective analysis, patients with tumors assigned to IGS-18 or classical GBMs had worse outcome than those assigned to IGS-22/23 when treated with a combination of bevacizumab and irrinotecan (45).…”