title: Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer.
abstract: OBJECTIVE
  Clinical trials have shown that adding bevacizumab to cytotoxic chemotherapy improves survival for patients with colorectal cancer, although its effectiveness in the Medicare population is uncertain.
  
  
  METHODS
  Using the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked database, we identified 2,526 patients with stage IV colorectal cancer diagnosed between 2002 and 2007 who received first-line combination chemotherapy with a fluoropyrimidine and either irinotecan (33%) or oxaliplatin (67%). Thirty-six percent of patients received bevacizumab with first-line therapy. The primary outcome was overall survival. Secondary outcomes were bevacizumab-associated toxicities, including the incidence of stroke, myocardial infarction, and GI perforation.
  
  
  RESULTS
  In the primary cohort inclusive of patients diagnosed between 2002 and 2007, bevacizumab with combination chemotherapy was associated with improved overall survival (adjusted hazard ratio [HR], 0.85; 95% CI, 0.78 to 0.93), although the effect was more modest when restricted to years 2004 to 2007 (HR, 0.93; 95% CI, 0.84 to 1.02). The observed survival advantage of bevacizumab was more apparent with irinotecan-based chemotherapy (HR, 0.80; 95% CI, 0.66 to 0.97) than with oxaliplatin-based chemotherapy (HR, 0.96; 95% CI, 0.86 to 1.07). Combination chemotherapy with bevacizumab, versus combination chemotherapy without bevacizumab, was associated with increased risk of stroke (4.9% v 2.5%, respectively; P < .01) and GI perforation (2.3% v 1.0%, respectively; P < .01). Cardiac events and venous thrombosis were not increased with bevacizumab.
  
  
  CONCLUSIONS
  The addition of bevacizumab to cytotoxic combination chemotherapy was associated with small improvement in overall survival as well as increased risk of stroke and perforation, but not cardiac events, among Medicare beneficiaries with stage IV colorectal cancer.
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. jmeyerhardt@partners.org
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Sanoff
authors.forename: William
authors.initials: W
authors.lastname: Carpenter
authors.forename: Deborah
authors.initials: D
authors.lastname: Schrag
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D015897:Comorbidity; D005260:Female; D006801:Humans; D007416:Intestinal Perforation / Q000453:epidemiology; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D006278:Medicare / Q000706:statistics & numerical data*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin