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

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

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27 Scopus citations

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 13.4months. 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 14.4months vs 10.6months 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.

Original languageEnglish (US)
Pages (from-to)726-734
Number of pages9
JournalPharmacoepidemiology and Drug Safety
Volume23
Issue number7
DOIs
StatePublished - Jul 2014

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Keywords

  • Bevacizumab
  • Colorectal cancer
  • Cumulative exposure
  • Observational study
  • Pharmacoepidemiology
  • Treatment beyond progression
  • Treatment patterns

ASJC Scopus subject areas

  • Epidemiology
  • Pharmacology (medical)

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