Combination of bevacizumab and chemotherapy for platinum-resistant recurrent ovarian cancer: some observations about the AURELIA trial.

Abstract

TO THE EDITOR: In the article by Pujade-Lauraine et al, published in Journal of Clinical Oncology on May 1, 2014, the authors stated that AURELIA (A Study of Bevaczumab [Avastin] Added to Chemotherapy in Patients With Platinum-Resistant Ovarian Cancer) is the first trial to demonstrate a significant progression-free survival benefit of either a combination regimen or a biologic agent in platinum-resistant ovarian cancer. This attractive result confirms that combining single-agent chemotherapy with biologic agents could be a novel strategy in the treatment of platinum-resistant disease. In our opinion, using the same bevacizumab dose (10 mg) in all three arms would have been preferable to administering the drug every 14 days, even in the topotecan arm (or 15 mg every 3 weeks in all three arms). A recent meta-analysis indicated that there was no significative difference between the high and low doses of bevacizumab, indicating that dose regimens may not alter the association of bevacizumab with risk of fatal adverse effects. In the AURELIA trial, patients who had received more than two prior anticancer regimens were ineligible. It is likely that almost all of the patients had received one or two lines of treatment with taxanes; therefore, we believe that in the study it would have been better to exclude the arm with paclitaxel, perhaps using another drug active in ovarian cancer. Moreover, a meta-analysis by Huang et al and another study found significant difference in risk of fatal adverse effects with bevacizumab when used in different chemotherapeutic regimens. Treatment with bevacizumab in combination with taxanes resulted in more toxic effects than bevacizumab combined with other agents. A randomized clinical trial comparing bevacizumab plus paclitaxel with bevacizumab plus capecitabine reported that the risk of chemotherapy discontinuation for adverse effects was twice as high with paclitaxel compared with capecitabine. The RIBBON-1 study (Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Chemotherapy With or Without Bevacizumab for First-Line Treatment of Human Epidermal Growth Factor Receptor 2-Negative, Locally Recurrent or Metastatic Breast Cancer) and a recent meta-analysis also confirmed that the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes. These data should advise against the use of taxanes in association with bevacizumab in secondor third-line chemotherapy schedules for platinum-resistant recurrent ovarian cancer. Also, if the safety data of AURELIA trial are favorable, it nevertheless would be interesting in this context to know, for example, what drugs and regimens caused the occurrence of fatal adverse effects in the two treatment arms (five deaths in each arm).