Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Fig 1.

Cohort definition. (*) Small percentage of patients will ultimately be diagnosed after death. FU, fluorouracil; HMO, health maintenance organization.

Fig 2.

Kaplan-Meier curves comparing overall survival for combination chemotherapy with or without bevacizumab (BEV): (A) either oxaliplatin or irinotecan with fluoropyrimidine (n = 1,484); (B) oxaliplatin with fluoropyrimidine (n = 781); (C) irinotecan with fluoropyrimidine (n = 703); and (D) subsets of irinotecan by fluoropyrimidine delivery. (*) n < 11; masked to protect patient confidentiality. FOLFIRI, fluorouracil, leucovorin, and irinotecan; FOLFOX, infusional fluorouracil, leucovorin, and oxaliplatin; IFL, irinotecan, fluorouracil, and leucovorin.