Schaub, Christina
Kebir, Sied
Junold, Nina
Hattingen, Elke
Schäfer, Niklas
Steinbach, Joachim P.
Weyerbrock, Astrid
Hau, Peter
Goldbrunner, Roland
Niessen, Michael
Mack, Frederic
Stuplich, Moritz
Tzaridis, Theophilos
Bähr, Oliver
Kortmann, Rolf-Dieter
Schlegel, Uwe
Schmidt-Graf, Friederike
Rohde, Veit
Braun, Christian
Hänel, Mathias
Sabel, Michael
Gerlach, Rüdiger
Krex, Dietmar
Belka, Claus
Vatter, Hartmut
Proescholdt, Martin
Herrlinger, Ulrich
Glas, Martin
Funding for this research was provided by:
This study was funded by Roche Pharma AG
Article History
Received: 11 April 2018
Accepted: 16 May 2018
First Online: 28 May 2018
Compliance with ethical standards
:
: Ulrich Herrlinger has served as a consultant for Roche, Novocure, Mundipharma, Noxxon and Bristol-Myers-Squibb. He has received a scientific grant from Roche and speakers honoraria from Roche, Medac, and Riemser Pharma. Martin Glas has served as a consultant for Roche, Novartis, Mundipharma, sigma tau and UCB Corporation. He has received speakers honoraria from Roche, Medac and sigma tau, and a scientific grant from Medac. Niklas Schäfer received honoraria from Roche. All other authors declare that they have no conflict of interest.
: GLARIUS was a randomized, controlled, unblinded, phase II trial (EudraCT No. 2009010390-21; ClinicalTrials.gov NCT00967330) approved by ethic committees of all participating centers. All patients gave written informed consent. All trial procedures adhered to the Declaration of Helsinki and the Guidelines of Good Clinical Practice. An independent data monitoring and safety board constantly reviewed all safety-relevant information.The trial was funded by Roche Pharmaceuticals. Data collection was performed by an independent clinical research organization funded by Roche. The principal investigator (U.H.) had full access to the data, reviewed all data, and had the final responsibility for manuscript submission.
: There is conflicting data as to whether angiogenesis inhibitors such as bevacizumab induce more distant and/or invasive recurrent tumors as compared to alkylating standard chemotherapy in malignant glioma. In recurrent glioblastoma, a radiographically determined increase in distant and infiltrative growth pattern has been linked to bevacizumab treatment. However, almost all these data stem from uncontrolled retrospective observations after failure of standard alkylating chemotherapy with temozolomide. Given bevacizumab treatment has become a standard in the recurrence scenario, it is important to shed light on this issue. To this end, we assessed the tumor growth patterns at first recurrence of patients in the GLARIUS trial, a randomized phase II trial comparing treatment with bevacizumab/irinotecan vs standard temozolomide in MGMT-non-methylated glioblastoma. We show that recurrence patterns (invasiveness and tumor growth) are similar in both groups, thus not supporting the hypothesis of a bevacizumab induced invasive or distant tumor recurrence phenotype.