% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Wirsching:142206, author = {H.-G. Wirsching and G. Tabatabai and U. Roelcke and A. F. Hottinger and F. Jörger and A. Schmid and L. Plasswilm and D. Schrimpf$^*$ and C. Mancao and D. Capper$^*$ and K. Conen and T. Hundsberger and F. Caparrotti and R. von Moos and C. Riklin and J. Felsberg and P. Roth and D. Jones$^*$ and S. Pfister$^*$ and E. J. Rushing and L. Abrey and G. Reifenberger and L. Held and A. von Deimling$^*$ and A. Ochsenbein and M. Weller}, title = {{B}evacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase {II} {ARTE} trial.}, journal = {Annals of oncology}, volume = {29}, number = {6}, issn = {1569-8041}, address = {Oxford}, publisher = {Oxford Univ. Press}, reportid = {DKFZ-2019-00020}, pages = {1423 - 1430}, year = {2018}, abstract = {The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT → TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population.ARTE was a 2 : 1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg×14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years. The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT. Response was assessed by RANO criteria. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses.Median PFS was longer in arm A than in arm B (7.6 and 4.8 months, P = 0.003), but OS was similar (12.1 and 12.2 months, P = 0.77). Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase (RTK) I methylation subtype (HR 0.25, P = 0.014) and proneural gene expression (HR 0.29, P = 0.025). In a Cox model of OS controlling for established prognostic factors, associations with more favorable outcome were identified for age <70 years (HR 0.52, P = 0.018) and Karnofsky performance score $90\%-100\%$ (HR 0.51, P = 0.026). Including molecular subtypes into that model identified an association of the RTK II gene methylation subtype with inferior OS (HR 1.73, P = 0.076).Efficacy outcomes and exploratory analyses of ARTE do not support the hypothesis that the addition of bevacizumab to RT generally prolongs survival in elderly glioblastoma patients. Molecular biomarkers may identify patients with preferential benefit from bevacizumab.NCT01443676.}, cin = {G380 / B062}, ddc = {610}, cid = {I:(DE-He78)G380-20160331 / I:(DE-He78)B062-20160331}, pnm = {315 - Imaging and radiooncology (POF3-315)}, pid = {G:(DE-HGF)POF3-315}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:29648580}, doi = {10.1093/annonc/mdy120}, url = {https://inrepo02.dkfz.de/record/142206}, }