Dataset Information

Influence of the American ODAC statement on Austrian bevacizumab prescribing practice for metastatic breast cancer.

ABSTRACT:

Background

Results of trial E2100 led to the accelerated approval of bevacizumab as first-line therapy for patients with metastatic breast cancer (MBC) in the U.S. in February 2008. Based on results from subsequent trials, the U.S. Food and Drug Administration Oncologic Drugs Advisory Committee (ODAC) issued a statement proposing to withdraw the license for bevacizumab in July 2010, whereas bevacizumab approval for MBC was not withdrawn in Europe. In this nationwide survey, we investigated the influence of the discrepancy between the ODAC and European Medicines Agency (EMA) positions on the prescription practice of bevacizumab for MBC in Austria during the period January 2006 to June 2011.

Methods

The absolute number of bevacizumab administrations for MBC patients per month in all Austrian hospitals within the mentioned time frame was retrieved from a comprehensive national database. Bevacizumab prescription numbers for other malignancies were retrieved in order to rule out that a change in bevacizumab prescribing practice might reflect general changes in Austrian health care policy.

Results

A steady increase in bevacizumab use was seen from January 2006 to June 2010 (42 versus 1,357 administrations per month) for MBC. Thereafter, a significant decline in bevacizumab prescriptions for MBC became evident, with numbers dropping to 842 in March 2011 and 662 in June 2011. Bevacizumab prescriptions showed only minor variations in control cohorts.

Conclusions

The Austrian bevacizumab prescribing practice in MBC patients was significantly influenced by the ODAC statement issued in July 2010, whereas the EMA position was accepted to a lesser degree.

SUBMITTER: Preusser M

PROVIDER: S-EPMC3399659 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Influence of the American ODAC statement on Austrian bevacizumab prescribing practice for metastatic breast cancer.

Preusser Matthias M Fülöp Gerhard G Berghoff Anna Sophie AS Heinzl Harald H Steger Guenther G GG Greil Richard R Zielinski Christoph C CC Bartsch Rupert R

The oncologist 20120627 7

<h4>Background</h4>Results of trial E2100 led to the accelerated approval of bevacizumab as first-line therapy for patients with metastatic breast cancer (MBC) in the U.S. in February 2008. Based on results from subsequent trials, the U.S. Food and Drug Administration Oncologic Drugs Advisory Committee (ODAC) issued a statement proposing to withdraw the license for bevacizumab in July 2010, whereas bevacizumab approval for MBC was not withdrawn in Europe. In this nationwide survey, we investigat ...[more]

PMID: 22744818

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Project description:Background: Biomarkers predicting response to bevacizumab in breast cancer are still missing. Since epigenetic modifications can contribute to an aberrant regulation of angiogenesis and treatment resistance, we investigated the influence of DNA methylation patterns on bevacizumab efficacy. Methods: Genome-wide methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip was performed in archival FFPE specimens of 36 patients with HER2-negative metastatic breast cancer treated with chemotherapy in combination with bevacizumab as first-line therapy (learning set). Based on objective response and progression-free survival (PFS) and considering ER expression, patients were divided in responders (R) and non-responders (NR). Significantly differentially methylated gene loci (CpGs) with a strong change in methylation levels (??>0.15 or ??<-0.15) between R and NR were identified and further investigated in 80 bevacizumab-treated breast cancer patients (optimization set) and in 15 patients treated with chemotherapy alone (control set) using targeted deep amplicon bisulfite sequencing. Methylated gene loci were considered predictive if there was a significant association with outcome (PFS) in the optimization set but not in the control set using Spearman rank correlation, Cox regression, and logrank test. Results: Differentially methylated loci in 48 genes were identified, allowing a good separation between R and NR (odds ratio (OR) 101, p<0.0001). Methylation of at least one cytosine in 26 gene-regions was significantly associated with progression-free survival (PFS) in the optimization set, but not in the control set. Using information from the optimization set, the panel was reduced to a 9-gene signature, which could divide patients from the learning set into 2 clusters, thereby predicting response with an OR of 40 (p<0.001) and an AUC of 0.91 (LOOCV). A further restricted 3-gene methylation model showed a significant association of predicted responders with longer PFS in the learning and optimization set even in multivariate analysis with an excellent and good separation of R and NR with AUC=0.94 and AUC=0.86, respectively. Conclusion: Both a 9-gene and 3-gene methylation signature can discriminate between R and NR to a bevacizumab-based therapy in MBC and could help identify patients deriving greater benefit from bevacizumab.

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Dataset Information

Influence of the American ODAC statement on Austrian bevacizumab prescribing practice for metastatic breast cancer.

Background

Methods

Results

Conclusions

Publications

Influence of the American ODAC statement on Austrian bevacizumab prescribing practice for metastatic breast cancer.

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