Originally published as JCO Early Release 10.1200/JCO.2008.16.3212 on October 14 2008

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Bevacizumab Beyond First Progression Is Associated With Prolonged Overall Survival in Metastatic Colorectal Cancer: Results From a Large Observational Cohort Study (BRiTE)

Axel Grothey, Mary M. Sugrue, David M. Purdie, Wei Dong, Daniel Sargent, Eric Hedrick, Mark Kozloff

From the Mayo Clinic Rochester, Rochester, MN; Genentech Inc, South San Francisco, CA; Ingalls Hospital, Harvey; and the University of Chicago, Chicago, IL

Corresponding author: Axel Grothey, MD, Division of Medical Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: grothey.axel{at}mayo.edu

Purpose Bevacizumab provides a survival benefit in first- and second-line metastatic colorectal cancer (mCRC). In a large, observational, bevacizumab treatment study (Bevacizumab Regimens: Investigation of Treatment Effects and Safety [BRiTE]) in patients who had mCRC, a longer-than-expected overall survival (OS) of 25.1 months was reported. The association between various pre- and post-treatment factors (including the use of bevacizumab beyond first progression [BBP]) and survival was examined.

Patients and Methods The 1,445 of 1,953 previously untreated patients with mCRC who were enrolled in BRiTE and who experienced disease progression (PD) were classified into three groups: no post-PD treatment (n = 253), post-PD treatment without bevacizumab (no BBP; n = 531), and BBP (n = 642). Relevant baseline and on-study variables, including BBP, were analyzed with a Cox model with respect to their independent effect on survival beyond first PD.

Results Median OS was 25.1 months (95% CI, 23.4 to 27.5 months), and median progression-free survival was 10.0 months in the overall BRiTE population. Baseline and postbaseline factors were well balanced between the BBP and no-BBP groups. Median OS rates were 12.6, 19.9, and 31.8 months in the no post-PD treatment, no-BBP, and BBP groups, respectively. In multivariate analyses, compared with no BBP, BBP was strongly and independently associated with improved survival (HR, 0.48; P < .001). Hypertension that required medication was the only bevacizumab-related safety event that occurred more frequently in the BBP group (24.6% v 19.2%).

Conclusion These results from a large, prospective, observational study suggest that continued vascular endothelial growth factor inhibition with bevacizumab beyond initial PD could play an important role improving the overall success of therapy for patients who have mCRC.

published online ahead of print at www.jco.org on October 13, 2008.

Supported by Genentech Inc.

Presented in part at the 43rd Annual American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; the 9th World Congress on Gastrointestinal Cancer, June 27-30, 2007, Barcelona, Spain; and the 14th European Cancer Conference, September 23-27, 2007, Barcelona, Spain.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00097578 [ClinicalTrials.gov]

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