Ulrich Herrlinger1, Niklas Schäfer2, Joachim P Steinbach2, Astrid Weyerbrock2, Peter Hau2, Roland Goldbrunner2, Franziska Friedrich2, Veit Rohde2, Florian Ringel2, Uwe Schlegel2, Michael Sabel2, Michael W Ronellenfitsch2, Martin Uhl2, Jaroslaw Maciaczyk2, Stefan Grau2, Oliver Schnell2, Mathias Hänel2, Dietmar Krex2, Peter Vajkoczy2, Rüdiger Gerlach2, Rolf-Dieter Kortmann2, Maximilian Mehdorn2, Jochen Tüttenberg2, Regine Mayer-Steinacker2, Rainer Fietkau2, Stefanie Brehmer2, Frederic Mack2, Moritz Stuplich2, Sied Kebir2, Ralf Kohnen2, Elmar Dunkl2, Barbara Leutgeb2, Martin Proescholdt2, Torsten Pietsch2, Horst Urbach2, Claus Belka2, Walter Stummer2, Martin Glas2. 1. Ulrich Herrlinger, Niklas Schäfer, Frederic Mack, Moritz Stuplich, Sied Kebir, Torsten Pietsch, and Martin Glas, University of Bonn, Bonn; Joachim P. Steinbach and Michael W. Ronellenfitsch, University of Frankfurt, Frankfurt; Astrid Weyerbrock and Horst Urbach, University of Freiburg, Freiburg; Peter Hau and Martin Uhl, University Hospital Regensburg, Regensburg; Roland Goldbrunner and Stefan Grau, University of Cologne, Cologne; Franziska Friedrich and Rolf-Dieter Kortmann, University of Leipzig, Leipzig; Veit Rohde, University of Goettingen, Goettingen; Florian Ringel, Klinikum rechts der Isar Technical University of Munich; Oliver Schnell and Claus Belka, Ludwig Maximillian University of Munich, Munich; Uwe Schlegel, Ruhr-Universität Bochum, Bochum; Michael Sabel and Jaroslaw Maciaczyk, University of Düsseldorf, Düsseldorf; Mathias Hänel, Klinikum Chemnitz, Chemnitz; Dietmar Krex, University of Dresden, Dresden; Peter Vajkoczy, Charité, Humboldt University of Berlin, Berlin; Rüdiger Gerlach, Helios Klinikum Erfurt, Erfurt; Maximilian Mehdorn, University of Kiel, Kiel; Jochen Tüttenberg, Klinikum Idar-Oberstein, Idar-Oberstein; Regine Mayer-Steinacker, University of Ulm, Ulm; Rainer Fietkau, University of Erlangen, Erlangen; Stefanie Brehmer, University of Mannheim, Mannheim; Ralf Kohnen and Elmar Dunkl, RPS Research Germany, Nürnberg; Barbara Leutgeb and Martin Proescholdt, Roche Pharma AG, Grenzach-Wyhlen; and Walter Stummer, University of Münster, Münster, Germany ulrich.herrlinger@ukb.uni-bonn.de. 2. Ulrich Herrlinger, Niklas Schäfer, Frederic Mack, Moritz Stuplich, Sied Kebir, Torsten Pietsch, and Martin Glas, University of Bonn, Bonn; Joachim P. Steinbach and Michael W. Ronellenfitsch, University of Frankfurt, Frankfurt; Astrid Weyerbrock and Horst Urbach, University of Freiburg, Freiburg; Peter Hau and Martin Uhl, University Hospital Regensburg, Regensburg; Roland Goldbrunner and Stefan Grau, University of Cologne, Cologne; Franziska Friedrich and Rolf-Dieter Kortmann, University of Leipzig, Leipzig; Veit Rohde, University of Goettingen, Goettingen; Florian Ringel, Klinikum rechts der Isar Technical University of Munich; Oliver Schnell and Claus Belka, Ludwig Maximillian University of Munich, Munich; Uwe Schlegel, Ruhr-Universität Bochum, Bochum; Michael Sabel and Jaroslaw Maciaczyk, University of Düsseldorf, Düsseldorf; Mathias Hänel, Klinikum Chemnitz, Chemnitz; Dietmar Krex, University of Dresden, Dresden; Peter Vajkoczy, Charité, Humboldt University of Berlin, Berlin; Rüdiger Gerlach, Helios Klinikum Erfurt, Erfurt; Maximilian Mehdorn, University of Kiel, Kiel; Jochen Tüttenberg, Klinikum Idar-Oberstein, Idar-Oberstein; Regine Mayer-Steinacker, University of Ulm, Ulm; Rainer Fietkau, University of Erlangen, Erlangen; Stefanie Brehmer, University of Mannheim, Mannheim; Ralf Kohnen and Elmar Dunkl, RPS Research Germany, Nürnberg; Barbara Leutgeb and Martin Proescholdt, Roche Pharma AG, Grenzach-Wyhlen; and Walter Stummer, University of Münster, Münster, Germany.
Abstract
PURPOSE: In patients with newly diagnosed glioblastoma that harbors a nonmethylated O(6)-methylguanine-DNA methyltransferase promotor, standardtemozolomide (TMZ) has, at best, limited efficacy. The GLARIUS trial thus explored bevacizumab plus irinotecan (BEV+IRI) as an alternative to TMZ. PATIENTS AND METHODS: In this phase II, unblinded trial 182 patients in 22 centers were randomly assigned 2:1 to BEV (10 mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10 mg/kg every 2 weeks) plus IRI(125 mg/m(2) every 2 weeks) or to daily TMZ (75 mg/m(2)) during RT followed by six courses of TMZ (150-200 mg/m(2)/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6). RESULTS: In the modified intention-to-treat (ITT) population, PFS-6 was increased from 42.6% with TMZ (95% CI, 29.4% to 55.8%) to 79.3% with BEV+IRI (95% CI, 71.9% to 86.7%; P <.001). PFS was prolonged from a median of 5.99 months (95% CI, 2.7 to 7.3 months) to 9.7 months (95% CI, 8.7 to 10.8 months; P < .001). At progression, crossover BEV therapy was given to 81.8% of all patients who received any sort of second-line therapy in the TMZ arm. Overall survival (OS) was not different in the two arms: the median OS was 16.6 months (95% CI, 15.4 to 18.4 months) with BEV+IRI and was 17.5 months (95% CI, 15.1 to 20.5 months) with TMZ. The time course of quality of life (QOL) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ) -C30 and QLQ-BN20 (which included cognitive functioning), of the Karnofsky performance score, and of the Mini Mental State Examination score was not different between the treatment arms. CONCLUSION:BEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ.
RCT Entities:
PURPOSE: In patients with newly diagnosed glioblastoma that harbors a nonmethylated O(6)-methylguanine-DNA methyltransferase promotor, standard temozolomide (TMZ) has, at best, limited efficacy. The GLARIUS trial thus explored bevacizumab plus irinotecan (BEV+IRI) as an alternative to TMZ. PATIENTS AND METHODS: In this phase II, unblinded trial 182 patients in 22 centers were randomly assigned 2:1 to BEV (10 mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10 mg/kg every 2 weeks) plus IRI(125 mg/m(2) every 2 weeks) or to daily TMZ (75 mg/m(2)) during RT followed by six courses of TMZ (150-200 mg/m(2)/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6). RESULTS: In the modified intention-to-treat (ITT) population, PFS-6 was increased from 42.6% with TMZ (95% CI, 29.4% to 55.8%) to 79.3% with BEV+IRI (95% CI, 71.9% to 86.7%; P <.001). PFS was prolonged from a median of 5.99 months (95% CI, 2.7 to 7.3 months) to 9.7 months (95% CI, 8.7 to 10.8 months; P < .001). At progression, crossover BEV therapy was given to 81.8% of all patients who received any sort of second-line therapy in the TMZ arm. Overall survival (OS) was not different in the two arms: the median OS was 16.6 months (95% CI, 15.4 to 18.4 months) with BEV+IRI and was 17.5 months (95% CI, 15.1 to 20.5 months) with TMZ. The time course of quality of life (QOL) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ) -C30 and QLQ-BN20 (which included cognitive functioning), of the Karnofsky performance score, and of the Mini Mental State Examination score was not different between the treatment arms. CONCLUSION:BEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ.
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Authors: Katharina J Wenger; Marlies Wagner; Se-Jong You; Kea Franz; Patrick N Harter; Michael C Burger; Martin Voss; Michael W Ronellenfitsch; Emmanouil Fokas; Joachim P Steinbach; Oliver Bähr Journal: Oncol Lett Date: 2017-05-25 Impact factor: 2.967
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