Herrlinger, Ulrich, Schaefer, Niklas, Steinbach, Joachim P., Weyerbrock, Astrid ORCID: 0000-0001-9060-4462, Hau, Peter ORCID: 0000-0003-3894-5053, Goldbrunner, Roland, Friedrich, Franziska, Rohde, Veit, Ringel, Florian, Schlegel, Uwe, Sabel, Michael, Ronellenfitsch, Michael W., Uhl, Martin, Maciaczyk, Jaroslaw, Grau, Stefan, Schnell, Oliver, Haenel, Mathias, Krex, Dietmar, Vajkoczy, Peter, Gerlach, Ruediger, Kortmann, Rolf-Dieter, Mehdorn, Maximilian, Tuettenberg, Jochen, Mayer-Steinacker, Regine, Fietkau, Rainer, Brehmer, Stefanie, Mack, Frederic, Stuplich, Moritz, Kebir, Sied, Kohnen, Ralf, Dunkl, Elmar, Leutgeb, Barbara, Proescholdt, Martin, Pietsch, Torsten, Urbach, Horst, Belka, Claus, Stummer, Walter and Glas, Martin (2016). Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O-6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J. Clin. Oncol., 34 (14). S. 1611 - 1623. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

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 (10mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10mg/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. (C) 2016 by American Society of Clinical Oncology

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Herrlinger, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinbach, Joachim P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weyerbrock, AstridUNSPECIFIEDorcid.org/0000-0001-9060-4462UNSPECIFIED
Hau, PeterUNSPECIFIEDorcid.org/0000-0003-3894-5053UNSPECIFIED
Goldbrunner, RolandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedrich, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rohde, VeitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ringel, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlegel, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabel, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ronellenfitsch, Michael W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uhl, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maciaczyk, JaroslawUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grau, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schnell, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haenel, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krex, DietmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vajkoczy, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlach, RuedigerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kortmann, Rolf-DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehdorn, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tuettenberg, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayer-Steinacker, RegineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fietkau, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brehmer, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mack, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stuplich, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kebir, SiedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohnen, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunkl, ElmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leutgeb, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Proescholdt, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietsch, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Urbach, HorstUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belka, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stummer, WalterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glas, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-275788
DOI: 10.1200/JCO.2015.63.4691
Journal or Publication Title: J. Clin. Oncol.
Volume: 34
Number: 14
Page Range: S. 1611 - 1623
Date: 2016
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ENDOTHELIAL GROWTH-FACTOR; PHASE-II; RECURRENT GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; STANDARD TREATMENT; MALIGNANT GLIOMA; OPEN-LABEL; GENE; RADIOTHERAPY; CONCOMITANTMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27578

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