Prognostic factors in recurrent glioblastoma patients treated with bevacizumab

Schaub, Christina; Tichy, Julia; Schäfer, Niklas; Franz, Kea; Mack, Frederic; Mittelbronn, Michel; Kebir, Sied; Thiepold, Anna-Luisa; Waha, Andreas; Filmann, Natalie; Banat, Mohammed; Fimmers, Rolf; Steinbach, Joachim P.; Herrlinger, Ulrich; Rieger, Johannes; Glas, Martin; Bähr, Oliver

doi:10.1007/s11060-016-2144-7

Cited by 23 publications

(14 citation statements)

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“…A number of patients from the cohort were included in previously published studies on the use of bevacizumab in recurrent glioblastoma (23)(24)(25).…”

Section: Methodsmentioning

confidence: 99%

Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine

et al. 2017

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Abstract. In previous trials, bevacizumab failed to prolong the overall survival time in newly diagnosed glioblastoma and at the first recurrence. Randomized clinical trials at the second or further recurrence following the failure of radiotherapy, temozolomide and lomustine, and retrospective analyses focusing on this specific cohort, are not yet available. A total of 62 patients with glioblastoma who received bevacizumab after the failure of standard care, including radiotherapy, temozolomide and lomustine, were retrospectively identified. Patient characteristics, previous treatment details, concomitant therapy, response based on the Response Assessment in Neuro-Oncology criteria, and progression-free survival (PFS) and overall survival (OS) times and rates were evaluated. Furthermore, the PFS and OS times and rates were analyzed for responders and non-responders. Of the patients, 54.8% (n=34) responded to treatment [complete response (CR) 3.2%, n=2; partial response (PR) 51.6%, n=32]. The median PFS time was 3.5 months and the median OS time was 7.5 months. The PFS rate at 6 months was 21.5% and the OS rate at 12 months was 11.5%. Responders (CR or PR) experienced a superior median PFS time compared with non-responders (i.e. stable or progressive disease; 5.4 vs. 1.9 months; P<0.0001) and a superior PFS rate at 6 months (34.9 vs. 7.1%; P<0.0001). The median OS time (8.6 vs. 6.4 months; P<0.0001) and OS rate at 12 months (21.3 vs. 0%; P<0.0001) were also superior in patients who exhibited a response to bevacizumab treatment. In conclusion, the objective response rate and the PFS and OS times and rates indicate that bevacizumab has activity in patients with glioblastoma following the failure of radiotherapy, temozolomide, and lomustine. A randomized trial comparing bevacizumab with best supportive care in these patients is advised.

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“…A number of patients from the cohort were included in previously published studies on the use of bevacizumab in recurrent glioblastoma (23)(24)(25).…”

Section: Methodsmentioning

confidence: 99%

Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine

et al. 2017

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“…However, due to the inherent multifocal tumor distribution, partial or total resection as compared to biopsy only at the time of initial diagnosis was more frequent in sGB than in mfGB (81% vs. 56%). Some patients of this case series were included in previously published studies on BEV therapy in recurrent glioblastoma [ 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Bevacizumab for Patients with Recurrent Multifocal Glioblastomas

Burger

Breuer

Cieplik

et al. 2017

IJMS

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In patients with glioblastoma, antiangiogenic therapy with bevacizumab (BEV) has been shown to improve progression-free survival (PFS), but not overall survival (OS). Especially in patients with an unusual infiltrative phenotype as seen in multifocal glioblastoma, the use of BEV therapy is still more controversial. Therefore, we prepared a retrospective case series with 16 patients suffering from a multifocal glioblastoma treated with BEV. We compared these patients to a matched control cohort of 16 patients suffering from glioblastoma with a single lesion treated with BEV. The objective of this study was to evaluate whether the course of disease differs in glioblastoma patients with a multifocal disease pattern compared to those with a single lesion only. Patients were treated with BEV monotherapy or BEV in combination with irinotecan or lomustine (CCNU). Response rates and PFS were similar in both groups. There was a trend for an unfavorable OS in the patient group with multifocal glioblastoma, which was expected due to the generally worse prognosis of multifocal glioblastoma. We investigated whether BEV therapy affects the invasive growth pattern as measured by the appearance of new lesions on magnetic resonance imaging (MRI). Under BEV therapy, there was a trend for a lower frequency of new lesions both in multifocal and solitary glioblastoma. Based on these results, BEV therapy at relapse appears to be justified to no lesser extent in multifocal glioblastoma than in solitary glioblastoma.

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“…Eleven studies were included to analyze the association between MGMT promoter methylation and survival in recurrent GBM patients ( 19 , 21 , 22 , 44 , 46 , 56 , 60 , 63 , 75 , 77 , 89 ). A significant improvement on OS and PFS was observed in methylated recurrent patients (OS: HR = 0.70, 95% CI 0.56–0.88, p < 0.001, I 2 = 61.4%; PFS: HR = 0.54, 95% CI 0.42–0.70, p < 0.001, I 2 = 54.8%, Figure S4 in Supplementary Material).…”

Section: Resultsmentioning

confidence: 99%

The Clinical Significance of O6-Methylguanine-DNA Methyltransferase Promoter Methylation Status in Adult Patients With Glioblastoma: A Meta-analysis

et al. 2018

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Background and objectivePromoter status of O6-methylguanine-DNA methyltransferase (MGMT) has been widely established as a clinically relevant factor in glioblastoma (GBM) patients. However, in addition to varied therapy schedule, the prognosis of GBM patients is also affected by variations of age, race, primary or recurrent tumor. This study comprehensively investigated the association between MGMT promoter status and prognosis in overall GBM patients and in different GBM subtype including new diagnosed patients, recurrent patients and elderly patients.MethodsA comprehensive search was performed using PubMed, EMBASE, Cochrane databases to identify literatures (published from January 1, 2005 to April 1, 2017) that evaluated the associations between MGMT promoter methylation and prognosis of GBM patients.ResultsTotally, 66 studies including 7,886 patients met the inclusion criteria. Overall GBM patients with a methylated status of MGMT receiving temozolomide (TMZ)-containing treatment had better overall survival (OS) and progression-free survival (PFS) [OS: hazard ratio (HR) = 0.46, 95% confidence interval (CI): 0.41–0.52, p < 0.001, Bon = 0.017; PFS: HR = 0.48, 95% CI 0.40–0.57, p < 0.001, Bon = 0.014], but no significant advantage on OS or PFS in GBM patients with TMZ-free treatment was observed (OS: HR = 0.97, 95% CI 0.91–1.03, p = 0.08, Bon = 1; PFS: HR = 0.76, 95% CI 0.57–1.02, p = 0.068, Bon = 0.748). These different impacts of MGMT status on OS were similar in newly diagnosed GBM patients, elderly GBM patients and recurrent GBM. Among patients receiving TMZ-free treatment, survival benefit in Asian patients was not observed anymore after Bonferroni correction (Asian OS: HR = 0.78, 95% CI 0.64–0.95, p = 0.02, Bon = 0.24, I2 = 0%; PFS: HR = 0.69, 95% CI 0.50–0.94, p = 0.02, Bon = 0.24). No benefit was observed in Caucasian receiving TMZ-free therapy regardless of Bonferroni adjustment.ConclusionThe meta-analysis highlights the universal predictive value of MGMT methylation in newly diagnosed GBM patients, elderly GBM patients and recurrent GBM patients. For elderly methylated GBM patients, TMZ alone therapy might be a more suitable option than radiotherapy alone therapy. Future clinical trials should be designed in order to optimize therapeutics in different GBM subpopulation.

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Prognostic factors in recurrent glioblastoma patients treated with bevacizumab

Cited by 23 publications

References 24 publications

Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine

Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine

Bevacizumab for Patients with Recurrent Multifocal Glioblastomas

The Clinical Significance of O6-Methylguanine-DNA Methyltransferase Promoter Methylation Status in Adult Patients With Glioblastoma: A Meta-analysis

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