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.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

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.