Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial

Abstract

Purpose: The National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time.

Patients and methods: Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point.

Results: Of 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value <.0001). The secondary end point of OS was no different between the two study arms for all patients (HR, 0.95; 95% CI, 0.79 to 1.13; P = .56) and for those with stage 3 disease (HR, 1.0; 95% CI, 0.83 to 1.21; P = .99).

Conclusion: Bevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.

Trial registration: ClinicalTrials.gov NCT00096278.

Fig 1.

CONSORT diagram. DFS, disease-free survival; mFF6, modified fluorouracil, leucovorin, and oxaliplatin for 6 months; mFF6 + Bev, mFF6 for 6 months plus bevacizumab for 12 months; OS, overall survival.

Fig 2.

Disease-free survival (DFS). Overall DFS for patients treated with modified fluorouracil, leucovorin, and oxaliplatin (mFF6) alone for 6 months or mFF6 for 6 months plus bevacizumab for 12 months (mFF6 + Bev). HR, hazard ratio.

Fig 3.

Overall survival for all patients treated with modified fluorouracil, leucovorin, and oxaliplatin (mFF6) alone for 6 months or mFF6 for 6 months plus bevacizumab for 12 months, (mFF6 + Bev). HR, hazard ratio.

Fig 4.

Survival after recurrence for patients relapsing (A) within the first 18 months after study entry and (B) relapsing 18 months after study entry. HR, hazard ratio; mFF6, modified fluorouracil, leucovorin, and oxaliplatin for 6 months; mFF6 + Bev, mFF6 for 6 months plus bevacizumab for 12 months.