Reference Detail

Ref Type

Journal Article

PMID

(26762204)

Authors

Erdem-Eraslan L, van den Bent MJ, Hoogstrate Y, Naz-Khan H, Stubbs A, van der Spek P, Böttcher R, Gao Y, de Wit M, Taal W, Oosterkamp HM, Walenkamp A, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, van der Holt B, Vernhout RM, Sillevis Smitt PA, Kros JM, French PJ

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer research	76	3	2016 Feb 01	525-34	Cancer Res

URL

Abstract Text

The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva), a humanized monoclonal antibody against circulating VEGF-A, when added to CCNU chemotherapy in patients with recurrent glioblastoma (GBM). In this study, we performed gene expression profiling (DASL and RNA-seq) of formalin-fixed, paraffin-embedded tumor material from participants of the BELOB trial to identify patients with recurrent GBM who benefitted most from beva+CCNU treatment. We demonstrate that tumors assigned to the IGS-18 or "classical" subtype and treated with beva+CCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit. In particular, expression of FMO4 and OSBPL3 was associated with treatment response. Importantly, the improved outcome in the beva+CCNU treatment arm was not explained by an uneven distribution of prognostically favorable subtypes as all molecular glioma subtypes were evenly distributed along the different study arms. The RNA-seq analysis also highlighted genetic alterations, including mutations, gene fusions, and copy number changes, within this well-defined cohort of tumors that may serve as useful predictive or prognostic biomarkers of patient outcome. Further validation of the identified molecular markers may enable the future stratification of recurrent GBM patients into appropriate treatment regimens.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
IDH1 mutant	glioblastoma	predicted - sensitive	Bevacizumab + Lomustine	Phase II	Actionable	In a retrospective analysis of a Phase II trial, IDH1 mutation correlated with favorable overall survival in recurrent glioblastoma patients treated with a combination of Avastin (bevacizumab) and Lomustine (PMID: 26762204).	26762204