title: Eligibility for bevacizumab as an independent prognostic factor for patients with advanced non-squamous non-small cell lung cancer: a retrospective cohort study.
abstract: BACKGROUND
  Bevacizumab requires some unique eligibility criteria, such as absence of hemoptysis and major blood vessel invasion by the tumor. The prognostic impact of these bevacizumab-specific criteria has not been evaluated.
  
  
  METHODS
  Patients with stage IIIB/IV, non-squamous non-small cell lung cancer who started chemotherapy before the approval of bevacizumab were reviewed. Patients with impaired organ function, poor performance status or untreated/symptomatic brain metastasis were excluded before the evaluation of bevacizumab eligibility. We compared overall survival and time to treatment failure among patients who were eligible (Group A) or ineligible (Group B) to receive bevacizumab.
  
  
  RESULTS
  Among 283 patients with stage IIIB/IV non-squamous non-small cell lung cancer, eligibility for bevacizumab was evaluated in 154 patients. Fifty-seven patients were considered ineligible (Group B) based on one or more of a history of hemoptysis (n = 20), major blood vessel invasion (n = 43) and cardiovascular disease (n = 8). The remaining 97 patients were classified into Group A. Overall survival was significantly better in Group A (median, 14.6 months) than in Group B (median, 7.1 months; p<0.0001). Time to treatment failure was also significantly longer in Group A (median, 6.9 months) than in Group B (median, 3.0 months; p<0.0001). Adjusted hazard ratios of bevacizumab eligibility for overall survival and time to treatment failure were 0.48 and 0.38 (95% confidence intervals, 0.33-0.70 and 0.25-0.58), respectively.
  
  
  CONCLUSIONS
  Eligibility for bevacizumab itself represents a powerful prognostic factor for patients with non-squamous non-small cell lung cancer. The proportion of patients who underwent first-line chemotherapy without disease progression or unacceptable toxicity can also be biased by bevacizumab eligibility. Selection bias can be large in clinical trials of bevacizumab, so findings from such trials should be interpreted with extreme caution.
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. ytakagi-tmd@umin.net
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takagi
authors.forename: Akira
authors.initials: A
authors.lastname: Toriihara
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Nakahara
authors.forename: Makiko
authors.initials: M
authors.lastname: Yomota
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuma
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosomi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibuya
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
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