Phase II study of everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer

Background: Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. Methods: In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. Results: Fifty patients were enrolled. Median age was 60.5 years (range 28-82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67 -42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. Conclusions: Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit. (C) 2019 Elsevier Inc. All rights reserved.