Avastin (chemical name: bevacizumab) is 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 chemotherapy. Avastin also is used to treat advanced-stage lung, colon, and kidney cancer. Avastin is given intravenously.
Metastatic breast cancer is cancer that has spread outside the breast to another part of the body.
The two studies reviewed here -- AVADO and RIBBON 2 -- suggest that treating metastatic breast cancer with Avastin and chemotherapy slightly increases the length of time women live without the cancer growing (called progression-free survival or PFS), but doesn't affect overall survival. These results were presented at the 2009 San Antonio Breast Cancer Symposium.
Avastin 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.
In the AVADO trial, women diagnosed with metastatic breast cancer got one of three treatments:
This was the first cancer treatment the women received (called first-line treatment by doctors). After about 2 years of follow-up, there were small differences in progression-free survival:
Though small, the differences in progression-free survival were statistically significant, which means that the difference was likely the result of the different treatments and not because of chance. Still, overall survival was essentially the same -- between 30 and 32 months -- no matter which treatment a woman received.
In the RIBBON 2 trial, women diagnosed with metastatic breast cancer were treated with one of several chemotherapy medicines alone or combined with one of two Avastin doses, depending on which chemotherapy was used. All the women already had received some type of treatment for the metastatic cancer, so the treatments being studied are called second-line treatments. There were small differences in progression-free survival:
The difference was statistically significant, which means that the difference was likely the result of the different treatments and not because of chance.
The results from both the AVADO and RIBBON 2 trials suggest that adding Avastin to chemotherapy to treat metastatic breast cancer can slightly increase the length of time a woman lives without the cancer growing. Still, adding Avastin to chemotherapy didn't increase the total amount of time a woman lived after treatment started compared to chemotherapy alone.
Based on these and other results, some doctors wonder if Avastin should be used routinely to treat metastatic breast cancer.
Some doctors are concerned that the benefits of Avastin don't outweigh the risk of side effects. 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.
Other doctors worry that the small benefits of Avastin don't justify its high cost: $30,000 to $40,000 per month. Depending on the type of insurance they have, some people receiving Avastin may have to pay part of this cost.
If you've been diagnosed with metastatic breast cancer, you and your doctor will develop a treatment plan that will likely include chemotherapy and possibly hormonal therapy and/or targeted therapy medicines such as Avastin. No matter which treatments are recommended, ask your doctor about:
With the most-up-to-date information, you and your doctor can decide on a treatment plan that makes the most sense for you and your unique situation.
You can learn more about Avastin, how it works, and how it is used to treat advanced-stage breast cancer in the Breastcancer.org Targeted Therapies section.
SAN ANTONIO (MedPage Today) -- Bevacizumab (Avastin) only modestly improves progression-free survival for metastatic breast cancer when added to chemotherapy, according to updated results of two trials.
The gain was statistically significant but averaged only one to two months compared with chemotherapy alone in the AVADO and RIBBON 2 trials as reported here at the San Antonio Breast Cancer Symposium.
Neither trial showed a significant survival advantage with the addition of the biologic agent.
Adam Brufsky, MD, PhD, of the University of Pittsburgh Cancer Institute, who presented the RIBBON 2 results at a press conference via phone due to a recently collapsed lung, called the benefit clinically meaningful.
But others, such as Mark Pegram, MD, of the University of Miami, weren't so impressed.
"Ordinarily in metastatic breast cancer we assess the response of our ongoing treatments every eight weeks for the average patients" with CT and bone scans, Pegram told MedPage Today.
"If you have a treatment effect that's shorter than that amount of time, then for practical purposes that's less than one restaging interval in our clinic," he explained, "which is bordering on clinical irrelevance."
Most of the clinical trial results thus far with bevacizumab support relatively modest treatment effects in the metastatic setting, including interim AVADO data and RIBBON 1, with the exception of the nearly six-month gain in progression-free survival seen in the E2100 trial.
Given the drug's expense -- roughly $30,000 to $40,000 a month -- Pegram said "it's definitely not a home run."
David W. Miles, MD, of Mount Vernon Hospital in Northwood, England, who presented the AVADO results, called this cost-benefit issue crucial but not part of his decision-making with patients.
"When I sit down with a patient I don't really have in my mind that, on average, a patient is going to get a two-month improvement in progression-free survival," he said at the press conference. "That is a number that is of some use in trying to establish the utility of a drug across populations. For the patient in front of me I will try to chose the regimen that is most likely to get the disease under control."
His group looked at median 25-month results of AVADO, which randomized first-line metastatic breast cancer patients to docetaxel (Taxotere) alone or in combination with bevacizumab at a dose of 7.5 or 15 mg/kg every three weeks.
The updated progression-free survival rate was nine months with the lower bevacizumab dose and 10 months with the higher dose compared with 8.1 months on docetaxel alone censored for off-protocol treatment before progression (hazard ratio 0.80, P=0.0450 and HR 0.67, P=0.0002, respectively).
Among secondary endpoints, objective response rates were 64.1%, 55.2%, and 46.4% (P=0.0739 and P=0.0003), respectively.
The overall survival at 25-month follow-up showed not even a trend for benefit (30.8, 30.2, and 31.9 months, P=0.7198 and P=0.8528, respectively).
The extensive crossover to bevacizumab treatment and other therapies with later lines of therapy may account for the lack of difference between groups in overall survival, Miles said.
Brufsky's RIBBON 2 trial was done in the second-line, HER2 negative or unknown, metastatic setting but showed similar results.
It randomized women to the investigator's choice of chemotherapy alone or with bevacizumab given at 10 mg/kg every two weeks or 15 mg/kg every three weeks depending on the chemotherapy regimen.
The event-driven analysis results Brufsky reported included:
Among the different chemotherapy regimens used in the trial, the taxanes and capecitabine (Xeloda) appeared to be more effective while gemcitabine (Gemzar) and vinorelbine (Navelbine) appeared less effective, Brufsky said.
Miles cautioned that the results he reported should be considered exploratory.
Brufsky warned that the overall survival data in his trial were still immature and that some of the subgroup analyses by chemotherapy type were based on small numbers.
Both noted the lack of additional toxicity with bevacizumab plus chemotherapy.
There had been concerns particularly with the docetaxel combination, Miles said. He called the findings reassuring. "This is a very safe way forward," he said.
AVADO was sponsored by F. Hoffman-La Roche.
Miles reported being on the speakers' bureau and consulting for Roche. Co-authors reported conflicts of interest with Roche and sanofi-aventis.
RIBBON 2 was sponsored by Genentech.
Brufsky reported recieving a research grant from, consulting for, and being on the speakers' bureau of Genetech. Co-authors reported conflicts of interest, including employment, with Genentech.
Pegram reported potential conflicts of interest with Genetech, GlaxoSmithKline, sanofi-aventis, and Amgen.
Primary source: San Antonio Breast Cancer Symposium Source reference: Brufsky A, et al "RIBBON-2: A randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of HER2-negative metastatic breast cancer" SABCS 2009; Abstract 42.Additional source: San Antonio Breast Cancer SymposiumSource reference: Miles DW, et al "Final overall survival (OS) results from the randomised, double-blind, placebo-controlled, phase III AVADO study of bevacizumab (BV) plus docetaxel (D) compared with placebo (PL) plus D for the first-line treatment of locally recurrent (LR) or metastatic breast cancer (MBC)" SABCS 2009; Abstract 41.
Breastcancer.org is a non-profit organization dedicated to providing information and community to those touched by this disease. Learn more about our commitment to providing complete, accurate, and private breast cancer information.
Breastcancer.org 7 East Lancaster Avenue, 3rd Floor Ardmore, PA 19003
©2011 Breastcancer.org - All rights reserved.
