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Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab.

ABSTRACT: Development of effective therapies for recurrent glioblastoma multiforme (GBM) and reliable, timely evaluation of their benefit are needed. Understanding the relationship between objective response (OR) and survival is important for determining whether OR can provide an early signal of treatment activity in clinical trials. We performed a landmark analysis to evaluate the association between OR and survival at 9, 18, and 26 weeks for 167 patients with recurrent GBM who participated in BRAIN, a phase II trial that evaluated efficacy of bevacizumab alone or in combination with irinotecan, using the Cox regression models adjusted for age, baseline Karnofsky performance score, first vs second relapse, and treatment arm. Hazard ratios (HRs) and P-values for survival between responders and nonresponders were calculated. Additional analyses were performed to test robustness, validity, fit, and accuracy of the models. The relationships between progression-free survival (PFS) and survival and between OR and PFS were also explored. There were 55 responders and 112 nonresponders across the 2 treatment arms in BRAIN. OR status at 9, 18, and 26 weeks was a statistically significant predictor of survival (HR ? 0.52, P < .01). PFS was also a statistically significant predictor of survival at each landmark (HR ? 0.25, P < .0001). The association between OR and PFS was not statistically significant, likely due to inadequate statistical power for the analysis. Clarifying the relationship of OR and survival is important for determining whether OR can be a reliable predictor of the benefit of a therapeutic agent in patients with recurrent GBM.

SUBMITTER: Prados M

PROVIDER: S-EPMC3018914 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab.

Prados Michael M Cloughesy Timothy T Samant Meghna M Fang Liang L Wen Patrick Y PY Mikkelsen Tom T Schiff David D Abrey Lauren E LE Yung W K Alfred WK Paleologos Nina N Nicholas Martin K MK Jensen Randy R Vredenburgh James J Das Asha A Friedman Henry S HS

Neuro-oncology 20101117 1

Development of effective therapies for recurrent glioblastoma multiforme (GBM) and reliable, timely evaluation of their benefit are needed. Understanding the relationship between objective response (OR) and survival is important for determining whether OR can provide an early signal of treatment activity in clinical trials. We performed a landmark analysis to evaluate the association between OR and survival at 9, 18, and 26 weeks for 167 patients with recurrent GBM who participated in BRAIN, a p ...[more]

PMID: 21084434

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Project description:BackgroundAnti-angiogenic therapy with bevacizumab is the most widely used treatment option for recurrent glioblastoma, but therapeutic response varies substantially and effective biomarkers for patient selection are not available. To this end, we determine whether novel quantitative radiomic strategies on the basis of MRI have the potential to noninvasively stratify survival and progression in this patient population.MethodsIn an initial cohort of 126 patients, we identified a distinct set of features representative of the radiographic phenotype on baseline (pretreatment) MRI. These selected features were evaluated on a second cohort of 165 patients from the multicenter BRAIN trial with prospectively acquired clinical and imaging data. Features were evaluated in terms of prognostic value for overall survival (OS), progression-free survival (PFS), and progression within 3, 6, and 9 months using baseline imaging and first follow-up imaging at 6 weeks posttreatment initiation.ResultsMultivariable analysis of features derived at baseline imaging resulted in significant stratification of OS (hazard ratio [HR] = 2.5; log-rank P = 0.001) and PFS (HR = 4.5; log-rank P = 2.1 × 10-5) in validation data. These stratifications were stronger compared with clinical or volumetric covariates (permutation test false discovery rate [FDR] <0.05). Univariable analysis of a prognostic textural heterogeneity feature (information correlation) derived from postcontrast T1-weighted imaging revealed significantly higher scores for patients who progressed within 3 months (Wilcoxon test P = 8.8 × 10-8). Generally, features derived from postcontrast T1-weighted imaging yielded higher prognostic power compared with precontrast enhancing T2-weighted imaging.ConclusionRadiomics provides prognostic value for survival and progression in patients with recurrent glioblastoma receiving bevacizumab treatment. These results could lead to the development of quantitative pretreatment biomarkers to predict benefit from bevacizumab using standard of care imaging.

Project description:Background and aimsThis retrospective review of patients with recurrent glioblastoma treated at the Preston Robert Tisch Brain Tumor Center investigated treatment patterns, survival, and safety with bevacizumab in a real-world setting.MethodsAdult patients with glioblastoma who initiated bevacizumab at disease progression between January 1, 2009, and May 14, 2012, were included. A Kaplan-Meier estimator was used to describe overall survival (OS), progression-free survival (PFS), and time to greater than or equal to 20% reduction in Karnofsky Performance Status (KPS). The effect of baseline demographic and clinical factors on survival was examined using a Cox proportional hazards model. Adverse event (AE) data were collected.ResultsSeventy-four patients, with a median age of 59 years, were included in this cohort. Between bevacizumab initiation and first failure, defined as the first disease progression after bevacizumab initiation, biweekly bevacizumab and bevacizumab/irinotecan were the most frequently prescribed regimens. Median duration of bevacizumab treatment until failure was 6.4 months (range, 0.5-58.7). Median OS and PFS from bevacizumab initiation were 11.1 months (95% confidence interval [CI], 7.3-13.4) and 6.4 months (95% CI, 3.9-8.5), respectively. Median time to greater than or equal to 20% reduction in KPS was 29.3 months (95% CI, 13.8-∞). Lack of corticosteroid usage at the start of bevacizumab therapy was associated with both longer OS and PFS, with a median OS of 13.2 months (95% CI, 8.6-16.6) in patients who did not initially require corticosteroids versus 7.2 months (95% CI, 4.8-12.5) in those who did (P = 0.0382, log-rank), while median PFS values were 8.6 months (95% CI, 4.6-9.7) and 3.7 months (95% CI, 2.7-6.6), respectively (P = 0.0243, log-rank). Treatment failure occurred in 70 patients; 47 of whom received salvage therapy, and most frequently bevacizumab/carboplatin (7/47; 14.9%). Thirteen patients (18%) experienced a grade 3 AE of special interest for bevacizumab.ConclusionsTreatment patterns and outcomes for patients with recurrent glioblastoma receiving bevacizumab in a real-world setting were comparable with those reported in prospective clinical trials.

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Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab.

Publications

Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab.

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