Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial

Herrlinger U, Schaefer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Haenel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tuettenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 34

Pages Range: 1611-9

Journal Issue: 14

DOI: 10.1200/JCO.2015.63.4691

Abstract

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.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).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.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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Mannheim Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) PRA Health Sciences United States (USA) (US) Roche Deutschland Holding GmbH Germany (DE) Albert-Ludwigs-Universität Freiburg Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Universitätsklinikum Regensburg Germany (DE) Universität zu Köln Germany (DE) Universität Leipzig Germany (DE) Georg-August-Universität Göttingen Germany (DE) Technische Universität München (TUM) Germany (DE) Ruhr-Universität Bochum (RUB) Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Klinikum Chemnitz Germany (DE) Technische Universität Dresden Germany (DE) Humboldt-Universität zu Berlin Germany (DE) HELIOS Kliniken Germany (DE) Christian-Albrechts-Universität zu Kiel Germany (DE) Saarland-Heilstätten GmbH Germany (DE) Universität Ulm Germany (DE)

How to cite

APA:

Herrlinger, U., Schaefer, N., Steinbach, J.P., Weyerbrock, A., Hau, P., Goldbrunner, R.,... Glas, M. (2016). Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. Journal of Clinical Oncology, 34(14), 1611-9. https://doi.org/10.1200/JCO.2015.63.4691

MLA:

Herrlinger, Ulrich, et al. "Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial." Journal of Clinical Oncology 34.14 (2016): 1611-9.

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