As the FDA considers whether to rescind approval for bevacizumab (Avastin) in the adjuvant setting, “disappointing” results from the GeparQuinto study indicate the agent may be best reserved for patients with triple-negative disease.
SAN ANTONIO-Bevacizumab (Avastin) has shown increased response rates and prolonged progression-free survival in combination with anthracyclines and taxanes in metastatic breast cancer. However, this agent does not appear to produce any clinically relevant increase in pathologic complete response in patients with early HER2-negative breast cancer in the neoadjuvant setting, according to the latest results from the GeparQuinto study.
“It was disappointing,” said lead investigator Gunter von Minckwitz, MD, PhD, in an interview with Oncology NEWS International. “I don’t see it being used in the neoadjuvant setting. There might be a place for it in treating triple-negative disease, which will be studied in other trials,” said Dr. von Minckwitz, who is managing director of the German Breast Group in Neu-Isenburg, Germany.
Bevacizumab is currently approved in the U.S. in combination with paclitaxel for the first-line treatment of metastatic breast cancer. In July 2010, an FDA advisory committee voted 12 to one to eliminate this indication from the treatment label of bevacizumab. The FDA is scheduled to issue a final ruling in mid-December.
In this randomized phase III trial, the researchers investigated whether adding bevacizumab to treatment with four cycles of epirubicin/cyclophosphamide (EC), followed by four cycles of docetaxel (Taxotere) improved the rate of pathologic complete response (pCR), which was defined as no invasive or noninvasive residual cancer in the breast or nodes. Between May 2007 and June 2010, 944 patients were assigned to EC followed by docetaxel and 945 patients to the same chemotherapy plus bevacizumab ( SABCS 2010 abstract S4-6).
The mean age of the patients who did not receive bevacizumab was 48 years and the mean age of the patients who did receive this agent was 49 years. Patients with untreated HER2-negative breast cancer were eligible for the trial if they had:
• Stage cT3/4a-d disease or
• Estrogen and progesterone receptor-negative disease (triple-negative) or
• ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1) disease
• No increased cardiac or bleeding risks.
After the first four cycles, an interim assessment found 24% of the patients treated without bevacizumab and 17% of patients treated with bevacizumab showed no response. These patients were discontinued from treatment. Interim safety data from the trial published earlier this year indicated that treatment with bevacizumab was feasible. Patients assigned to it experienced more leukopenia, infections, mucositis, and hypertension but less edema. This safety profile is no different from that reported in first-line metastatic trials or phase II adjuvant trials of bevacizumab, according to Dr. von Minckwitz.
The effect of bevacizumab might be restricted to the triple-negative subtype in this setting, Dr. von Minckwitz said. He noted that results from other studies (NSABP B-40, BEATRICE) and long-term survival from the current trial have to be awaited before any definite conclusions can be drawn.
“The original aim of antiangiogenic drugs is to stop the new growth, which is very different from what we did in our trial. So this approach is quite different. It looks like there is no need to use it in the early disease setting,” Dr. von Minckwitz said. “The main problem is that we don’t have a predictive marker and so it is used in every patient. A predictive marker would allow us to better know which patients would benefit.”