title: FDA drug approval summary: bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer.
abstract: On June 20, 2006, the U.S. Food and Drug Administration (FDA) approved bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), administered in combination with FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin) for the second-line treatment of metastatic carcinoma of the colon or rectum. Efficacy and safety were demonstrated in one Eastern Cooperative Oncology Group (ECOG) open-label, multicenter, randomized, three-arm, active-controlled trial enrolling 829 adult patients. Patients had received a fluoropyrimidine- and irinotecan-based regimen as initial therapy for metastatic disease; or they had received prior adjuvant irinotecan-based chemotherapy and had recurred within 6 months of completing therapy. Treatments included bevacizumab, 10 mg/kg, as a 90-minute i.v. infusion on day 1, every 2 weeks, either alone or in combination with FOLFOX4, or FOLFOX4 alone. The bevacizumab monotherapy arm was closed to accrual after an interim efficacy analysis suggested a possibly shorter survival in that arm. Overall survival (OS), the primary study endpoint, was significantly longer for patients receiving bevacizumab in combination with FOLFOX4 than for those receiving FOLFOX4 alone. The objective response rate was significantly higher in the FOLFOX4 plus bevacizumab arm than in the FOLFOX4 alone arm. The duration of response was approximately 6 months for both treatment arms. Patients treated with the bevacizumab combination were also reported, based on investigator assessment, to have significantly longer progression-free survival. There were no new bevacizumab safety signals. The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound-healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, and congestive heart failure.
authors.affiliation: Division of Biological Oncology Products, Office of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration, HFD-150, 5600 Fishers Lane, Rockville, Maryland 20857, USA. cohenma@cder.fda.gov
authors.forename: Martin H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Joe
authors.initials: J
authors.lastname: Gootenberg
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D017277:Drug Approval; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil