The study reviewed here found that women diagnosed with metastatic HER2-negative breast cancer (cancer that has spread beyond the breast to another part of the body) treated with a high dose of Avastin (chemical name: bevacizumab) and Taxotere (chemical name: docetaxel) lived about 2 months longer without the cancer growing compared to women treated with only Taxotere.
Avastin is a targeted therapy that works by blocking the growth of new blood vessels that cancer cells depend on to grow and function. A protein called vascular endothelial growth factor (VEGF) makes new blood vessels grow in cancer cells. Avastin blocks the VEGF protein.
Avastin is currently approved by the U.S. Food and Drug Administration to be used in combination with Taxol (chemical name: paclitaxel) to treat people with metastatic HER2-negative breast cancer who haven't yet received any chemotherapy. Avastin also is used to treat advanced-stage lung, colon, and kidney cancer. Avastin is given intravenously.
Taxotere is a type of taxane chemotherapy.
In this study, called the AVADO (Avastin and Docetaxel) trial, 736 women diagnosed with metastatic HER2-negative breast cancer got one of three treatments:
This was the first treatment for metastatic breast cancer the women had received. Doctors call this first-line treatment.
After about 2 years of follow-up, compared to the women who got only Taxotere, the women who got the high-dose Avastin and Taxotere:
Still, all three groups of women lived for about the same amount of time (called overall survival): between 30 and 31 months.
Using a low dose (instead of a high dose) of Avastin in combination with Taxotere did improve the length of time before the cancer started growing -- 9 months, compared to about 8 months with Taxotere alone -- but this difference wasn't statistically significant. This means that the difference could be due to chance and not because of the difference in treatment.
Because adding Avastin to Taxotere didn't improve overall survival, some doctors are concerned the benefits may not outweigh the risk of side effects and the high cost of Avastin. Other doctors think that a greater response rate and a longer time until the cancer starts growing are important, even if overall survival doesn't improve. Common side effects of Avastin include high blood pressure, nosebleeds, and extra protein in the urine. People treated with Avastin also may have weakness, pain, and diarrhea. Avastin also may cause other serious side effects, including a higher risk of stroke or heart problems, kidney malfunction, and reduced white blood cell count.
If you've been diagnosed with metastatic HER-negative breast cancer, you and your doctor will develop a treatment plan that probably will include chemotherapy and possibly hormonal therapy and targeted therapy medicines such as Avastin. No matter which treatments you're considering, it's a good idea to talk your doctor about:
With the most-up-to-date information, you and your doctor can create a treatment plan that makes the most sense for you and your unique situation.
You can learn more about Avastin in the Breastcancer.org Targeted Therapies section.
(MedPage Today) -- 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 coauthors 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: 2666-2676). 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: 4966-4972).
Miles and coauthors 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.
The AVADO trial was sponsored by F. Hoffmann-La Roche.
Miles disclosed relationships with Roche. Other authors disclosed relationships with Roche, sanofi-aventis, GlaxoSmithKline, and Novartis. The authors included an employee of Roche.
Primary source: Journal of Clinical Oncology Source reference: Miles DW et al. "Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer" J Clin Oncol 2010; DOI: 10.1200/JCO.2008.21.6457.
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