Literature DB >> 24830357

Bevacizumab exposure beyond first disease progression in patients with metastatic colorectal cancer: analyses of the ARIES observational cohort study.

Axel Grothey1, E Dawn Flick, Allen L Cohn, Tanios S Bekaii-Saab, Johanna C Bendell, Mark Kozloff, Nancy Roach, Yong Mun, Susan Fish, Herbert I Hurwitz.   

Abstract

PURPOSE: This analysis from Avastin® Registries: Investigation of Effectiveness and Safety (ARIES) examined the association between exposure to bevacizumab after disease progression (PD) and postprogression survival (PPS) in bevacizumab-exposed metastatic colorectal cancer (mCRC) through the application of time-dependent and time-fixed analytical methods.
METHODS: Patients with mCRC who were treated with first-line bevacizumab and who survived first PD (PD1) were included. A time-dependent Cox regression model was fitted to assess the effect of cumulative bevacizumab exposure on PPS, while controlling for potential confounders. In addition to support findings from previous studies, a modified intent-to-treat (mITT) analysis compared PPS in patients who received bevacizumab beyond disease progression (BBP) with those who did not (No-BBP).
RESULTS: Of 1550 patients, 1199 survived PD1 and had a median PPS of 13.4 months. Cumulative bevacizumab exposure was associated with improved PPS (p = 0.0040). After adjusting for confounders, the hazard ratios (HRs) for PPS decreased, on average, by 1.2% (range, 1.1-1.3%) with each additional dose of bevacizumab. In the mITT analysis, the median PPS for BBP (n = 438) was 14.4 months vs 10.6 months with for No-BBP (n = 667). BBP was found to be independently associated with longer PPS in a multivariable Cox regression analysis (HR, 0.84; 95% confidence interval, 0.73-0.97). Protocol-specified adverse events suspected to be associated with bevacizumab occurred in 13.0% of patients with BBP.
CONCLUSION: This analysis supports the observation that bevacizumab exposure after PD1 is associated with longer PPS in mCRC.
Copyright © 2014 John Wiley & Sons, Ltd.

Entities:  

Keywords:  bevacizumab; colorectal cancer; cumulative exposure; observational study; pharmacoepidemiology; treatment beyond progression; treatment patterns

Mesh:

Substances:

Year:  2014        PMID: 24830357     DOI: 10.1002/pds.3633

Source DB:  PubMed          Journal:  Pharmacoepidemiol Drug Saf        ISSN: 1053-8569            Impact factor:   2.890


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