title: Effectiveness of bevacizumab exposure beyond disease progression in patients with non-small-cell lung cancer: analyses of the ARIES observational cohort study.
abstract: Bevacizumab used in combination with first-line chemotherapy confers an overall survival (OS) benefit for patients with non-squamous non-small-cell lung cancer (NSCLC). This analysis from the ARIES observational cohort study (OCS) was initiated to evaluate the effect of bevacizumab use beyond disease progression (BBP) on clinical outcomes in patients with NSCLC receiving first-line treatment with bevacizumab and chemotherapy.
  
  
  
  The ARIES OCS prospectively enrolled patients from 2006 to 2009 in the United States who had advanced non-squamous NSCLC, received bevacizumab with chemotherapy in the first-line setting, and survived progressive disease (PD). A dichotomous landmark analysis examined post-PD OS (ppOS) in patients who received BBP versus no BBP within 30 days post PD. A time-dependent Cox model assessed the effect of cumulative BBP exposure on ppOS.
  
  
  
  The ARIES OCS enrolled 1967 patients with first-line NSCLC; 1358 patients had first PD and were alive at the 30-day landmark (351 patients with BBP and 1007 patients with no BBP). The landmark analysis showed that BBP was associated with a lower risk of death (BBP versus No-BBP); hazard ratio [HR], 0.75; 95% confidence interval 0.65-0.86. In the cumulative exposure analysis of 1461 patients who had PD, HRs for ppOS decreased by approximately 4% for each additional 21-day interval of bevacizumab received. Protocol-specified bevacizumab-select adverse events occurred in 14% of BBP patients.
  
  
  
  BBP was associated with a lower risk of death in patients with NSCLC treated with first-line bevacizumab and chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of US Medical Affairs, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Leon
authors.affiliation: Department of Oncology, Scripps Clinic, La Jolla, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kosty
authors.affiliation: Department of Internal Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jahanzeb
authors.affiliation: Department of Oncology, Sarah Cannon Research Institute, Nashville, TN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Spigel
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
authors.forename: Antoinette J
authors.initials: AJ
authors.lastname: Wozniak
authors.affiliation: Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Brahmer
authors.affiliation: Department of US Medical Affairs, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Fish
authors.affiliation: Department of US Medical Affairs, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: E Dawn
authors.initials: ED
authors.lastname: Flick
authors.affiliation: Department of US Medical Affairs, Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hazard
authors.affiliation: Department of Oncology, Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
keywords: bevacizumab; non-small-cell lung cancer; observational cohort study; pharmacoepidemiology; treatment beyond progression