A novel strategy of knocking down tumor vasculature and keeping it from getting back up significantly reduced the risk of tumor progression among women with recurrent ovarian, tubal or peritoneal cancers, investigators reported.
Among 107 women enrolled in a randomized phase II trial, the combination of the experimental vascular-disrupting agent fosbretabulin with the angiogenesis inhibitor bevacizumab (Avastin) was associated with a median progression-free survival (PFS, the primary endpoint) of 7.3 months, compared with 4.8 months for bevacizumab alone. The hazard ratio (HR) for the combination was 0.69 (P = .05), reported Dr. Bradley J. Monk of Creighton University, Omaha, Neb., and Dignity Health St. Joseph’s Hospital and Medical Center, Phoenix, and his colleagues.
Dr. Bradley J. Monk
“This randomized phase II trial comparing bevacizumab plus fosbretabulin to bevacizumab alone provides further evidence regarding the safety and efficacy of nonchemotherapy-containing antivascular combinations,” they wrote (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.65.8153).
Combining a vascular-disrupting agent such as fosbretabulin with an agent targeted against vascular endothelial growth factor (VEGF) such as bevacizumab allows for more selective disruption of tumor vessels and inhibition of tumor neovascularization, while largely sparing cells with normal vasculature.
The regimen has the theoretical advantage of lower toxicity than more conventional combinations of an anti-VEGF agent and cytotoxic chemotherapy compounds. In a phase I trial of fosbretabulin and becavizumab, hypertension appeared to be the major dose-limiting toxicity, the authors noted.
In this phase II study, women with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma were randomly assigned to receive bevacizumab 15 mg/kg IV once every 3 weeks or the same dose and schedule of bevacizumab plus fosbretabulin 60 mg/m2 IV until disease progression or intolerable toxicity.
As noted before, the study met its primary endpoint of an improvement in PFS with the combination. Among patients with measurable disease, the overall response rate to the combination was 35.7%, compared with 28.2% for bevacizumab alone.
The only grade 3 or greater adverse event occurring more frequently with the combination than with single-agent bevacizumab was hypertension, which occurred in 35% vs. 20%, respectively. One patient in the combination arm had a grade 3 thromboembolic event and one patient in the bevacizumab-only arm had an intestinal fistula.
“On the basis of the PFS, overall response rate, and tolerability of these two antivascular therapies, further evaluation is warranted for this chemotherapy-free regimen,” Dr. Monk and his associates said.
The study was supported by grants from the National Cancer Institute. Dr. Monk and several coauthors disclosed consulting/advisory roles, speaker’s bureau participation, research funding, or travel reimbursements from multiple pharmaceutical companies.