Avastin Helpful in Treatment of Stage IV
Although we all agree that the news is not good enough (it will only be good enough when breast cancer can always be cured or, even better, prevented), there is a lot of encouraging research about the treatment of Stage IV/metastatic/advanced breast cancer. This is a summary from Med Page about the value of adding Avastin to Taxotere in the treatment of women with advanced disease. Adding this targeted drug resulted in a 23% improvement in the time to further progression of the cancer. Again, not good enough, but definitely a step in the right direction. This is also more proof that identification of targeted treatments is our future.
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Targeted Drug Slows Breast Cancer Progression
By Charles Bankhead, Staff Writer, MedPage Today
May 28, 2010
MedPage Today Action Points
Explain to patients that adding a targeted drug to chemotherapy slowed progression of advanced breast cancer by two months compared with chemotherapy alone.
Women with advanced breast cancer had significant improvement in progression-free survival when bevacizumab (Avastin) was added to docetaxel (Taxotere), investigators in a multicenter clinical trial reported.
Progression-free survival increased by two months with bevacizumab 15 mg/kg plus docetaxel compared with docetaxel plus placebo, David W. Miles, MD, of Mount Vernon Hospital in Middlesex, England, and co-authors wrote online in the Journal of Clinical Oncology.
A lower dose of the angiogenesis inhibitor resulted in a nonsignificant improvement compared with docetaxel alone.
The addition of bevacizumab did not substantively affect the safety profile of docetaxel.
"The benefit of combining bevacizumab with docetaxel was also seen in the secondary endpoints of overall response rate, duration of response, and time to treatment failure," Miles and colleagues wrote.
Taken with the positive results of an earlier study of the combination, "these data suggest that the combination of bevacizumab with taxane chemotherapy should be considered as an option for the first-line treatment of HER2-negative metastatic breast cancer," they added.
The published report adds confirmation to abstracts of the study reported last year at the American Society of Clinical Oncology meeting and the San Antonio Breast Cancer Symposium.
Interest in combining bevacizumab and docetaxel has been stoked by positive results from a study of bevacizumab-paclitaxel therapy in patients with locally advanced or metastatic breast cancer (N Engl J Med 2007; 357: 2666-76). An independent review of the data showed a 52% reduction in the hazard for progression or death, and the response rate doubled compared with that of paclitaxel alone (J Clin Oncol 2009; 2: 4966-72).
Miles and co-authors reported findings from the phase III Avastin and Docetaxel (AVADO) trial, which involved 736 women with untreated HER2-negative, locally advanced, or metastatic breast cancer.
All the women received docetaxel and were randomized to placebo or to one of two doses of bevacizumab -- 7.5 or 15 mg/kg.
The primary endpoint was progression-free survival, and secondary endpoints included overall response rate, duration of response, time to treatment failure, overall survival, and safety.
When the trial ended, the combination of bevacizumab and docetaxel led to a 23% improvement in progression-free survival for all bevacizumab-treated patients combined compared with the placebo group (HR 0.77, P=0.006). The lower dose of bevacizumab had a less pronounced effect (HR 0.86, P=0.12).
In a stratified analysis that excluded patients who received nonprotocol therapy before disease progression, the lower dose of bevacizumab was associated with a 20% improvement in the hazard (HR 0.80, P=0.045), and the higher dose led to a 33% reduction in the hazard (HR 0.67, P<0.001).
Median progression-free survival was 8.1 months in the placebo arm, 9.0 months with the lower dose of bevacizumab, and 10.0 months with the other dose of the angiogenesis inhibitor. The higher dose of bevacizumab significantly improved the response rate compared with placebo (64% versus 46.4%, P<0.001) but the lower dose did not (55%, P=0.07). Median time to treatment failure was 6.6 months with placebo, 7.7 months with 7.5 mg/kg bevacizumab (NS), and 8.0 months with 15 mg/kg (P=0.02).
Overall survival was 30 to 31 months in all three treatment groups.
The published article did not address the cost-effectiveness of the bevacizumab-docetaxel combination, a question that arose during the San Antonio meeting. Various sources cited cost estimates ranging from $7,000 to $40,000 per month for adding bevacizumab to docetaxel.
Primary source: Journal of Clinical Oncology