Sceintific Programme

OS02  Featured Orals
OVARY

09-Nov-2014 14:00 15:30
 
 
Abstract:
RANDOMIZED PHASE 2 EVALUATION OF BEVACIZUMAB VERSUS BEVACIZUMAB/FOSBRETABULIN IN RECURRENT OVARIAN, TUBAL OR PERITONEAL CARCINOMA: A GYNECOLOGIC ONCOLOGY GROUP STUDY
Aims
The Vascular disrupting agent (VDA) fosbretabulin tromethamine selectively targets pre-existing tumor vasculature causing vascular shutdown leading to cell death and necrosis. Anti-angiogenesis agents like bevacizumab, a humanized anti-VEGF monoclonal antibody, might prevent revascularization after/during VDA treatment.
Methods
Patients with recurrent/persistent epithelial ovarian, tubal, or peritoneal carcinoma; measurable or detectable disease; and < 3 prior regimens  were randomized to bevacizumab (15 mg/kg IV q 3weeks) or bevacizumab (15 mg/kg) + fosbretabulin (60 mg/m2) IV every 3 weeks until disease progression or  toxicity.  Randomization was stratified by disease status (measurable vs. non-measurable), prior bevacizumab, and platinum-free interval. The primary endpoint was progression-free survival (PFS).  The study was designed with 80% power at a 10% level of significance to detect a hazard ratio (HR) reduction of 37.5%.
Results
The study enrolled 107 patients. Median PFS was 4.8 and 7.3 months for bevacizumab and bevacizumab+ fosbretabulin, respectively (HR = 0.685; 90% 2-sided CI=0.47 ~1.00). The proportion responding to bevacizumab was 28.2% (90% CI 16.7 ~ 42.3%) among 39 patients with measurable disease and 35.7% (90% CI 23.5 ~ 49.5%) among 42 patients treated with the combination. Adverse events (> grade 2) were more common in the combination particularly hypertension (35% versus 16%). There was one grade 3 thromboembolic event with the combination.  One intestinal perforation in the bevacizumab arm was observed.
Conclusion
Based on the PFS and tolerability of these two anti-vascular therapies, further evaluation is warranted for this chemotherapy-free regimen. Fosbretabulin in combination with bevacizumab may double the risk of hypertension.
 
Co-authors
B. Monk1, M. Sill2, J. Walker3, P. DiSilvestro4, G. Sutton5, K. Tewari6, E. Pajon7, L. Martin8, J. Schilder9, R. Coleman10, J. Balkssoon11, C. Aghajanian12.
1Division of Gynecologic Oncology, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital & Medical Center, Phoenix, USA.
2Gynecologic Oncology, NRG Oncology, Buffalo, USA.
3Division of Gynecologic Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
4Division of Gynecologic Oncology, Women & Infants Hospital, Providence, USA.
5Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, USA.
6Division of Gynecologic Oncology, University of California Irvine, Orange, USA.
7Gynecologic Oncology, Colorado Cancer Research Program CCOP, Denver, USA.
8Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, USA.
9Division of Gynecologic Oncology, Indiana University Medical Center, Indianapolis, USA.
10Division of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
11Oncology, Oxigene Inc., San Francisco, USA.
12Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA.