Survival and quality of life in the randomized, multicenter GLARIUS trial investigating bevacizumab/irinotecan versus standard temozolomide in newly diagnosed, MGMT-non-methylated glioblastoma patients.

Herrlinger, Ulrich; Schaefer, Niklas; Steinbach, Joachim P.; Weyerbrock, Astrid; Hau, Peter; Goldbrunner, Roland; Friedrich, Franziska; Rohde, Veit; Ringel, Florian; Braun, Christian; Kohnen, Ralf; Leutgeb, Barbara; Belka, Claus; Urbach, Horst; Stummer, Walter; Glas, Martin

doi:10.1200/jco.2014.32.15_suppl.2042

Cited by 12 publications

(20 citation statements)

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“…Over the years, seven phase II (including two randomized) 11 – 17 and three phase III randomized studies 18 – 20 with BVZ as part of the treatment of newly diagnosed GBM patients have been published. In three studies, BVZ was given as neoadjuvant treatment, 11 , 12 , 14 while it was given as concomitant and adjuvant treatment in combination with RT in the remaining studies 13 , 15 – 20 ( Table 1 ). The response rates were comparable in both the neoadjuvant and adjuvant setting, and 23% to 38% responded to treatment, which is comparable to patients treated for recurrent disease.…”

Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

“…Finally, median OS varied from 11.7 to 23 months. The studies 11 – 20 varied in baseline characteristics such as patient age, performance status, degree of surgical resection, steroid use, and epigenetic silencing of MGMT (O6-methylguanine-DNA methyltransferase), which have been shown previously to have prognostic value, 33 , 34 and this may explain some of the observed variations in response, PFS, and OS.…”

Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

“…Among the published studies 11 – 20 were two randomized Phase III studies, AVAGlio 18 and RTOG 0825, 19 which compared standard treatment versus standard treatment plus BVZ. Both studies included newly diagnosed GBM patients in good performance status having MGMT methylated as well as non-methylated tumors.…”

Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

“…In addition to the above, a third Phase III randomized study, GLARIUS, has been published, in which standard treatment was compared to RT combined with concomitant and adjuvant BVZ, plus irinotecan. 20 The study included non-methylated MGMT GBMs only, who are patients with supposedly worse prognoses as compared to patients with methylated MGMT. The data showed increased median OS in both arms as compared to published data from non-methylated groups, 35 which indicates that some sort of selection other than MGMT methylation status might have occurred.…”

Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

“…Several phase II studies in GBM patients with recurrent disease have shown impressive response rates varying from 30% to 50%, prolongation of life in responders, as well as improved quality of life (QOL). 6 – 10 These studies have led to a number of investigations in newly diagnosed GBM patients, 11 – 17 including well conducted prospective randomized phase III trials 18 – 20 testing the hypothesis that GBM patients for first line therapy should be treated with standard multimodality treatment in combination with BVZ. In this paper we will discuss the results of these recent investigations of combining BVZ and standard treatment in newly diagnosed patients with primary GBM.…”

Section: Introductionmentioning

confidence: 99%

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The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

Poulsen¹,

Urup²,

Michaelsen³

et al. 2014

CMAR

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Glioblastoma multiforme (GBM) remains one of the most devastating tumors, and patients have a median survival of 15 months despite aggressive local and systemic therapy, including maximal surgical resection, radiation therapy, and concomitant and adjuvant temozolomide. The purpose of antineoplastic treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results of these studies along with relevant preclinical data will be described, and pitfalls in clinical and paraclinical endpoints will be discussed.

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Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

Section: Bvz In Newly Diagnosed Gbmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

Poulsen¹,

Urup²,

Michaelsen³

et al. 2014

CMAR

View full text Add to dashboard Cite

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Treatment Considerations for MGMT-Unmethylated Glioblastoma

Taylor

Schiff

2014

Curr Neurol Neurosci Rep

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Prognosis for patients with glioblastoma continues to be limited, despite an aggressive, multimodal treatment including alkylating chemotherapy. Temozolomide, the most widely used alkylating agent in glioblastoma, is cytotoxic to cells by inducing DNA damage but can be rapidly repaired by the protein O (6)-methylguanine DNA methyltransferase (MGMT). In a subset of glioblastomas, the MGMT promoter is methylated, impairing the repair mechanism and conferring chemosensitivity. However, MGMT is overexpressed in 60 % of glioblastomas providing an inherent resistance to alkylating agents and challenging the role of temozolomide in this population. This article reviews the data establishing MGMT promoter methylation as a prognostic factor in glioblastoma and its potential role as a predictor of temozolomide response. It focuses on results from recent studies in newly diagnosed glioblastoma, and the role of temozolomide in MGMT-unmethylated patients. We then turn the discussion to alternatives to temozolomide for newly diagnosed patients as well as therapeutic options at the time of recurrence.

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Pharmacologic Therapies for Malignant Glioma: A Guide for Clinicians

et al. 2014

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This review covers the medical options for malignant gliomas based on the results of recent clinical trials and updated information on molecular markers of prognostic and predictive value. In addition to alkylating agents, the antiangiogenic drug bevacizumab is increasingly used, particularly in cases of recurrence. Supportive care, including antiedema agents, antiepileptic drugs and anticoagulants, represent complementary treatment approaches of the utmost clinical importance.

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Survival and quality of life in the randomized, multicenter GLARIUS trial investigating bevacizumab/irinotecan versus standard temozolomide in newly diagnosed, MGMT-non-methylated glioblastoma patients.

Cited by 12 publications

References 0 publications

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

Treatment Considerations for MGMT-Unmethylated Glioblastoma

Pharmacologic Therapies for Malignant Glioma: A Guide for Clinicians

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