Bevacizumab in Stage II-III Colon Cancer: 5-Year Update of the National Surgical Adjuvant Breast and Bowel Project C-08 Trial

• Published in: Journal of clinical oncology Vol. 31; no. 3; pp. 359 - 364
• Main Authors: ALLEGRA, Carmen J, YOTHERS, Greg, O'CONNELL, Michael J, SHARIF, Saima, PETRELLI, Nicholas J, LOPA, Samia H, WOLMARK, Norman
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.01.2013
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Bevacizumab; Biological and medical sciences; Colonic Neoplasms - drug therapy; Colonic Neoplasms - mortality; Disease-Free Survival; Female; Fluorouracil - administration & dosage; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Cancer; Humans; Leucovorin - administration & dosage; Male; Medical sciences; Middle Aged; Neoplasm Staging; Organoplatinum Compounds - administration & dosage; Original Reports; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Antineoplastic agent; Digestive system; Gut; Early stage; Monoclonal antibody; Malignant tumor; Bevacizumab; Colonic disease; Colon cancer; Cancerology; Vascular endothelium growth factor; Treatment; Surgery; Digestive diseases; Intestinal disease; Clinical trial; Locally advanced stage; Mammary gland; Antiangiogenic agent; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2012.44.4711

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 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. 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). 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.