ORLANDO, FLA. — Adding the antiangiogenic agent bevacizumab to standard chemotherapies for breast cancer produced significant survival gains in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.
The results were hailed both as a step into the mainstream of cancer treatment for targeted agents and as an advance likely to change the standard of care for breast cancer.
Bevacizumab, a monoclonal antibody, blocks vascular endothelial growth factor (VEGF), preventing the growth of blood vessels that feed tumors. The Food and Drug Administration approved the drug last year for the treatment of advanced colorectal cancer when used in combination with a chemotherapy regimen consisting of irinotecan plus 5-fluorouracil (5-FU) and leucovorin.
The antiangiogenic strategy, proposed in 1971 by Judah Folkman, M.D., of Children's Hospital Boston (N. Engl. J. Med. 1971;285:1182–6), was long doubted by many in the oncology community. That began to change in 2003, with the report of a 5-month survival advantage with the addition of bevacizumab to standard therapy for advanced colorectal cancer.
Genentech Inc., the maker of Avastin, supported the study. The company also is supporting clinical trials of the drug in ovarian, renal cell, and other cancers.
In the first interim report from the first trial of an antiangiogenic agent for breast cancer, bevacizumab has so far improved overall survival 33% for patients who received the agent in addition to standard first-line therapy with paclitaxel for locally recurrent or metastatic breast cancer. The multicenter trial randomized 350 patients to the bevacizumab-paclitaxel combination and 365 to standard treatment.
Principal investigator Kathy Miller, M.D., said although the data are still early, progression-free survival and response were clearly improved.
Dr. Miller of Indiana University Cancer Center in Indianapolis reported that median progression-free survival was 11.0 months in the bevacizumab-paclitaxel arm, compared with 6.1 months for women who only were treated with paclitaxel (hazard ratio 0.50). She said 28.2% responded to the combination therapy, but only 14.2% responded to paclitaxel alone.
Although 13.3% of bevacizumab patients were treated for grades 3 and 4 hypertension, Dr. Miller said side effects were manageable. Bleeding occurred in fewer than 1% and proteinuria in 2.5% of the bevacizumab patients.
Grade 3 neuropathy also was more common with bevacizumab, occurring in 19.9%, versus 13.6% of the control arm.
Commenting on the trial, Eric P. Winer, M.D., said unanswered questions include whether continuing on bevacizumab might be beneficial, and for how long.
Dr. Winer of Dana-Farber Cancer Institute in Boston said treating a breast cancer patient with bevacizumab costs $4,000 biweekly, or $104,800 for a year. He based his estimate on 95% of the wholesale price and a patient body weight of 60 kg, adding colon cancer treatment requires half the dose used in the breast cancer trial, sponsored by the National Cancer Institute and conducted by ECOG.