Bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-methylguanine-DNA methyltransferase nonmethylated glioblastoma: the randomized GLARIUS trial
PurposeIn patients with newly diagnosed glioblastoma that harbors a nonmethylated O6-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 M...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 14, 2016
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| In: |
Journal of clinical oncology
Year: 2016, Volume: 34, Issue: 14, Pages: 1611-1619 |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.2015.63.4691 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1200/JCO.2015.63.4691 Verlag, Volltext: https://ascopubs.org/doi/10.1200/JCO.2015.63.4691 
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| Author Notes: | Ulrich Herrlinger, Niklas Schäfer, Joachim P. Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Franziska Friedrich, Veit Rohde, Florian Ringel, Uwe Schlegel, Michael Sabel, Michael W. Ronellenfitsch, Martin Uhl, Jaroslaw Maciaczyk, Stefan Grau, Oliver Schnell, Mathias Hänel, Dietmar Krex, Peter Vajkoczy, Rüdiger Gerlach, Rolf-Dieter Kortmann, Maximilian Mehdorn, Jochen Tüttenberg, Regine Mayer-Steinacker, Rainer Fietkau, Stefanie Brehmer, Frederic Mack, Moritz Stuplich, Sied Kebir, Ralf Kohnen, Elmar Dunkl, Barbara Leutgeb, Martin Proescholdt, Torsten Pietsch, Horst Urbach, Claus Belka, Walter Stummer, and Martin Glas |
| Summary: | PurposeIn patients with newly diagnosed glioblastoma that harbors a nonmethylated O6-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 MethodsIn 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/m2 every 2 weeks) or to daily TMZ (75 mg/m2) during RT followed by six courses of TMZ (150-200 mg/m2/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6).ResultsIn 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.ConclusionBEV+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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| Item Description: | Gesehen am 02.12.2019 Im Titel ist "6" hochgestellt |
| Physical Description: | Online Resource |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.2015.63.4691 |