GUARNERI PAPER
IAN E SMITH, MD: From anecdotal statements, the story was emerging that if you were on bevacizumab therapy along with bisphosphonates, then there was an increased risk of osteonecrosis of the jaw. Given the mechanism of action of bevacizumab, that was a plausible hypothesis.
What we have done in our study is to examine two randomized trials that I am not involved in and a large safety study of about 2,200 patients called ATHENA, which I’ve been leading. The three trials examined patients with breast cancer who were receiving bevacizumab. We’ve pooled the different study populations so there’s a database now of well over 3,000 patients. Our results show that there is no increased risk of developing osteonecrosis of the jaw in patients receiving bevacizumab and bisphosphonates compared to patients receiving bisphosphonates alone. This is a story that didn’t stand up. Whatever the cons of bevacizumab may be, increased risk of osteonecrosis of the jaw is not one of them.
GOLSHAN PAPER
DR BRUFSKY: This report came from a partnership of surgeons and medical oncologists at Dana-Farber. The authors reported on two separate Phase II trials — one evaluating neoadjuvant chemotherapy and the other evaluating neoadjuvant chemotherapy with bevacizumab — for patients with triple-negative breast cancer.
This was an interesting idea, though I was a bit concerned that it was not a randomized comparison. The response rate in the trial in which patients received a platinum agent alone was about 49 percent, and the response rate in the trial in which patients received a platinum agent and bevacizumab was about 80 percent. Though pathologic complete response rates were not reported, that’s a very high response rate with the addition of bevacizumab.
Additionally, there appeared to be more downstaging and more breast-conserving surgery — 57 percent in the platinum/bevacizumab trial versus 46 in the platinum-only trial. Of concern in the platinum/bevacizumab trial was the fact that of eight women who underwent reconstructions, four actually lost their reconstructions — three saline expanders and one silicone implant. Clearly wound dehiscence occurred in four of the eight women.
This was not a statistically significant difference as these were two separate Phase II trials and not one randomized Phase II analysis, but nonetheless, I believe this paper is important because it is almost a “shot across the bow” to let us know that we have to be careful if we’re going to administer bevacizumab in the neoadjuvant setting. I believe that’s something we need to strongly consider.
Prof Smith is Professor of Cancer Medicine in the Breast Unit of the Department of Medicine of The Royal Marsden Hospital in London and Surrey, United Kingdom.
Dr Brufsky is Associate Professor of Medicine and Associate Division Chief of Hematology/Oncology at the University of Pittsburgh, Co-Director of the Comprehensive Breast Cancer Center and Associate Director for Clinical Investigation at the University of Pittsburgh Cancer Institute in Pittsburgh, Pennsylvania.
