CHICAGO, June 2 -- In recurrent or metastatic breast cancer, bevacizumab (Avastin) significantly improved progression-free survival when added to docetaxel (Taxotere), a multicenter European study showed.
Compared with the taxane alone, docetaxel plus bevacizumab improved progression-free survival by 30% to 40%, depending upon the dose of the antiangiogenic agent, David Miles, M.D., of Mount Vernon Cancer Center in Middlesex, England, reported at the American Society of Clinical Oncology meeting here.
Action Points
- Explain to patients who ask that the addition of bevacizumab, a drug that blocks blood vessel development, to taxane chemotherapy may reduce the risk of progression in breast cancer.
- Emphasize that the findings are early and not final and that the treatment regimen remains investigational.
- Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
The findings also suggested that a higher dose of bevacizumab led to more improvement in progression-free survival.
"I think we can conclude that there is a clinical benefit of adding first-line bevacizumab to taxane chemotherapy for patients with HER2-negative disease," Dr. Miles said at a press briefing.
The findings came from a multinational phase III trial involving 736 women with locally recurrent or metastatic HER2-negative breast cancer with no prior treatment for metastatic disease. All patients received docetaxel at a dose of 100 mg/m2 and were randomized to placebo or to 7.5 or 15 mg/kg of bevacizumab. Treatment with docetaxel continued for a maximum of nine cycles, and placebo or bevacizumab was continued until progression.
After a median follow-up of about a year, patients randomized to either dose of bevacizumab had significant improvement in progression-free survival in unstratified and stratified analyses.
In the unstratified analysis, the lower and higher doses of bevacizumab were associated hazard ratios of 0.79 (P=0.0138) and 0.72 (P=0.0099) versus placebo. Stratified analysis resulted in a hazard ratio of 0.69 (P=0.0035) for the lower dose of bevacizumab and 0.61 (P=0.0001) for the higher dose.
A preliminary analysis of overall survival (a secondary endpoint) showed nonsignificant improvement of 8% and 32% with the lower and higher doses of bevacizumab, but Dr. Miles emphasized that the data remain immature for assessment of overall survival. The final analysis of overall survival will occur in 2009.
Bevacizumab led to significantly higher response rates of 55% (P=0.0295) for the lower dose and 63% (P=0.001) for the higher dose compared with 44% for placebo.
The study was not designed to compare the two bevacizumab doses, making a comparison of the two arms "statistically difficult," said Dr. Miles.
Nevertheless he added, "My assessment of the situation from the data we have available is that the 15 mg/kg every three weeks is probably the favored dose."
Asked whether he would be uncomfortable with using the lower dose, Dr. Miles said, "I suppose insofar as you are seeing a benefit in the low-dose group and are seeing a difference in response rate, the low dose would appear to be better than getting nothing at all, but I suspect that if you wanted to get the maximum effect, you would go to the higher dose."
Commenting on the dose issue, Eric Winer, M.D., of Harvard, who moderated the press briefing, noted that "in U.S. the approved dose of bevacizumab to be given in conjunction with paclitaxel [Taxol] is that higher dose." Paclitaxel is a taxane similar to docetaxel.
The addition of bevacizumab to docetaxel resulted in no new or unexpected safety issues, as overall rates of adverse events, serious adverse events, and adverse events leading to discontinuation of docetaxel, placebo, or bevacizumab were similar across treatment groups.
| One or more authors acknowledged various relationships with Roche, which sponsored the study, and with sanofi-aventis. |
Primary Source
American Society of Clinical Oncology
Source Reference: Miles D, et al "Randomized, double-blind, placebo-controlled phase III study of bevacizumab (BV) with edocetaxel (D) or docetaxel with placebo (PL) as first-lline therapy for patients wit locally recurrent or metastatic berast cancer (mBC): AVADO" ASCO Meeting 2008; Abstract LBA1011.