Data evaluated by an independent review committee revealed that the addition of bevacizumab to trastuzumab and docetaxel significantly improved progression-free survival in HER2-positive breast cancer, despite findings from an investigator assessment that the improvement was present but statistically non-significant.
Luca Gianni, M.D., director of medical oncology at the San Raffaele Cancer Center in Milano, Italy, presented results from AVEREL, a randomized, phase 3 trial, at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011. The trial is designed to evaluate bevacizumab combined with trastuzumab and docetaxel as first-line therapy for HER2-positive, locally recurrent/metastatic breast cancer. The study is the first randomized trial of bevacizumab in this type of breast cancer, according to the researchers.
Patients had measurable or evaluable HER2-positive, locally recurrent/metastatic breast cancer and Eastern Cooperative Oncology Group performance status 0/1 and had not received prior chemotherapy for advanced disease. Patients with central nervous system metastases were excluded.
Researchers enrolled 424 patients from 60 centers during September 2006 to February 2010, with 421 patients receiving treatment. They randomly assigned patients to receive trastuzumab and docetaxel (n=208) or to receive trastuzumab and docetaxel plus bevacizumab (n=216).
At a median follow-up of 26 months, investigator assessment revealed an 18 percent reduction in risk of progression or death with the addition of bevacizumab compared with that of patients who received only trastuzumab and docetaxel. However, an independent review committee analysis found a 28 percent reduction in risk for progression or death with the addition of bevacizumab. Overall, median progression-free survival increased by 2.8 and 2.9 months with bevacizumab according to investigator analysis and independent review committee analysis, respectively.
Gianni said that because there are effective treatments for women with HER2-positive breast cancer, researchers are now examining the precise role of an anti-angiogenic drug in combination with existing therapy.
"The concept of this trial was a test for the benefit observed in early phase 1 and phase 2," Gianni said. "In a way, we confirmed that combining an anti-angiogenic and [other treatment] is a good idea. But now, we have to search the subset of women who have the characteristics associated with benefit from addition of an anti-angiogenic. The key element is looking for a restricted indication that might have a longer-lasting effect than we can observe in AVEREL."
Biomarkers will be important in helping determine the best role for bevacizumab in treating HER2-positive cases, he said.
"The limit in anti-angiogenic therapy is that we treat all participants and we have no hint of what are the tumor characteristics or the patient characteristics that deserve intervention with anti-angiogenic therapy," Gianni said. "We have started some study investigation of biomarkers, and we hope that the AVEREL results, together with other studies, can help in finding ways of restricting indication of bevacizumab to those who could have the right benefit."