Avastin Improves Chemo for Refractory HER2-Negative Breast Cancer
In cases of refractory HER2-negative breast cancer, adding bevacizumab (Avastin) to common chemotherapies improves progression-free survival, randomized trial data show.
The data are from the RIBBON-2 trial, conducted in women who needed second-line chemotherapy for metastatic breast cancer. Adding bevacizumab to their chemo did not improve their overall survival, as was originally reported several years ago.
But for women with human epidermal growth factor receptor (HER)-2-negative metastatic disease, bevacizumab delayed disease progression and so might still “expand the treatment options,” said lead investigator Dr. Adam M. Brufsky of the University of Pittsburgh in an email to Reuters Health.
In an October 11th online paper in the Journal of Clinical Oncology, Dr. Brufsky and colleagues reported on 684 women who had previously received at least one cytotoxic treatment for local or distant spread of their HER2-negative tumors.
In RIBBON-2 they each received either a capecitabine-, taxane-, gemcitabine-, or vinorelbine-based chemotherapy regimen, and in addition the researchers randomly assigned them 2:1 to receive bevacizumab or placebo.
Median progression-free survival was 7.2 months in the bevacizumab group and 5.1 months in placebo patients, a significant difference. The objective response rate was also better with bevacizumab, although not significantly so (39.5% vs 29.6%).
One year survival rates were similar in the two arms of the study (69.5% vs 66.2%).
The proportion of women who withdrew from the study due to adverse effects was nearly twice as high in the intervention group (13.3% vs 7.2%). Serious adverse events were also more common with bevacizumab (24.5% vs 17.6%). However, there was no difference in the number of treatment-emergent deaths due to adverse events. The most common cause of death was disease progression.
“Taken together,” the investigators conclude, “these data provide a rationale for adding bevacizumab to second-line cytotoxic therapy for patients with HER2-negative metastatic breast cancer.”
Bevacizumab, however, has had trouble retaining its approval for metastatic breast cancer in the US.
Bevacizumab initially received accelerated approval in 2008, but its efficacy was questioned and follow-up has not shown a survival improvement. In June of this year a U.S. Food and Drug Administration advisory panel ruled against use of the drug, which reportedly costs about $88,000 per patient per year.
Genentech, which makes the drug for Roche, has appealed and a final decision is expected from the FDA later this year.
Meanwhile, insurers in the U.S., among them Blue Shield of California, have stopped routinely covering new prescriptions for breast cancer patients.
In Europe too, there has been less controversy. Bevacizumab was approved there for use in combination with paclitaxel in 2007. Earlier this year European regulators reversed a previous decision and expanded its use to include administration in combination with capecitabine.
Doctors themselves are divided on the agent, with about 40% of those who responded to a small survey saying that they would continue to use the drug even if the FDA finally rejects it (see Reuters Health report of October 26, 2011).
The study by Dr. Brufsky and colleagues was supported by Genentech of South San Francisco, California. Dr. Brufsky acted in an advisory or consultant capacity but received no compensation from the company. A number of other authors received research funding or are employed by Genentech.