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

Abstract

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.

• Authors: Lale Erdem-Eraslan, Martin J van den Bent, Youri Hoogstrate, Hina Naz-Khan, Andrew Stubbs, Peter van der Spek, René Böttcher, Ya Gao, Maurice de Wit, Walter Taal, Hendrika M Oosterkamp, Annemiek Walenkamp, Laurens V Beerepoot, Monique C J Hanse, Jan Buter, Aafke H Honkoop, Bronno van der Holt, René M Vernhout, Peter A E Sillevis Smitt, Johan M Kros, Pim J French
• Journal: Cancer research (Cancer Res) Vol. 76 Issue 3 Pg. 525-34 (Feb 01 2016) ISSN: 1538-7445 [Electronic] United States
• PMID: 26762204 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Angiogenesis Inhibitors
• Bevacizumab
• Lomustine

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Bevacizumab (administration & dosage)
• Brain Neoplasms (diagnosis, drug therapy, genetics)
• Female
• Gene Expression Profiling
• Glioblastoma (diagnosis, drug therapy, genetics)
• Humans
• Lomustine (administration & dosage)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (diagnosis, drug therapy)