On November 10, 2014 OXiGENE reported the first presentation at a scientific conference of the positive results from the Phase 2 GOG 186I study of fosbretabulin combined with bevacizumab in recurrent ovarian, tubal and peritoneal carcinoma (Filing 8-K , OXiGENE, NOV 10, 2014, View Source [SID:1234500958]). The detailed data were presented by the Gynecologic Oncology Group (GOG), now part of NRG Oncology, in an oral presentation at the 15th Biennial Meeting of the International Gynecologic Cancer Society (IGCS) meeting held in Melbourne, Australia.
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The study achieved its primary endpoint and demonstrated a statistically significant increase in progression-free survival (PFS) for the combination as compared to bevacizumab alone (p=0.049; HR=0.685). The study enrolled 107 patients with both platinum-sensitive and platinum-resistant recurrent ovarian cancer at 67 clinical sites in the United States. Median PFS was 7.3 months for bevacizumab plus fosbretabulin (n=54) compared to 4.8 months with bevacizumab (n= 53).
"This is the first randomized trial to demonstrate a potential clinical benefit from the combination of a vascular disrupting agent with an anti-angiogenic agent in ovarian cancer," said Bradley J. Monk, M.D., FACS, FACOG, principal investigator for the trial, and Professor and Director, Division of Gynecologic Oncology and Department of Obstetrics and Gynecology at the University of Arizona Cancer Center. "Given the significant need for new treatment options in recurrent ovarian cancer, we are extremely encouraged by the results of this study that combine two anti-vascular agents without chemotherapy. We believe that additional evaluation of the benefits of combined fosbretabulin and bevacizumab in ovarian cancer patients is strongly warranted."
In a post-hoc subgroup analysis, data showed that patients who were platinum-resistant also had a statistically significant improvement in PFS with the combination. Among these 27 patients, median PFS was 6.7 months for those on bevacizumab and fosbretabulin compared to 3.4 months for those receiving bevacizumab alone (p=0.01; HR=0.57). Although the subgroup included a relatively small number of patients, these findings suggest that adding fosbretabulin to bevacizumab has a potentially greater effect in this difficult-to-treat patient group than for platinum-sensitive patients.
"We believe that these compelling data show fosbretabulin has a meaningful benefit in recurrent ovarian cancer, particularly in platinum-resistant patients who have extremely limited treatment options," said Dai Chaplin, Ph.D., OXiGENE’s President and CEO. "We now look forward to discussing these findings with the regulatory agencies to determine a potential path forward for fosbretabulin in ovarian cancer."
Patients with measurable disease who received the combination of fosbretabulin and bevacizumab may achieve a higher objective response rate (ORR), a secondary endpoint in the study measured according to RECIST criteria. Although not a statistically significant result, patients receiving the combination had an ORR of 35.7 percent (n=42) compared to 28.2 percent for patients on bevacizumab alone (n=39). In the small subgroup of platinum-resistant patients, the addition of fosbretabulin to bevacizumab treatment increased ORR to 40 percent (n=10) compared to 12.5 percent (n=8) for bevacizumab.
Additional secondary endpoints in the study included safety and overall survival. All treatment- related adverse events in the study were manageable, with one Grade 4 event occurring in each treatment arm. Consistent with prior clinical experience with fosbretabulin, patients in the combination arm experienced an increased incidence of Grade 3 hypertension compared to the control arm (10 cases for bevacizumab as compared to 17 for the combination). All cases of hypertension were managed with antihypertensive treatments, as specified in the study protocol.
Patients continue to be followed for overall survival. A preliminary analysis of 33 events did not demonstrate a difference in overall survival between the study arms. Further analysis of this secondary endpoint will be conducted as the data matures.