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

Publication

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

Journal Paper/Review - Mar 14, 2016

Herrlinger Ulrich, Kortmann Rolf-Dieter, Mehdorn Maximilian, Tüttenberg 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, Gerlach Rüdiger, Vajkoczy Peter, Schäfer Niklas, Steinbach Joachim P, Weyerbrock Astrid, Hau Peter, Goldbrunner Roland, Friedrich Franziska, Rohde Veit, Ringel Florian, Schlegel Uwe, Sabel Michael, Ronellenfitsch Michael W, Uhl Martin, Maciaczyk Jaroslaw, Grau Stefan, Schnell Oliver, Hänel Mathias, Krex Dietmar, Glas Martin

Citation

Herrlinger U, Kortmann R, Mehdorn M, Tüttenberg 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, Gerlach R, Vajkoczy P, Schäfer N, Steinbach J, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch M, Uhl M, Maciaczyk J, Grau S, Schnell O, Hänel M, Krex D, Glas M. Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol 2016; 34:1611-9.

Type

Journal Paper/Review (English)

Journal

J Clin Oncol 2016; 34

Publication Date

Mar 14, 2016

Issn Electronic

1527-7755

Pages

1611-9

Brief description/objective

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.