A Phase Ii Study Of Intermittent Sorafenib With Bevacizumab In Bevacizumab-Naive Epithelial Ovarian Cancer (Eoc) Patients.

5019 Background: We targeted the VEGF pathway at multiple points by combining the VEGFR2/Raf kinase inhibitor sorafenib (S) with bevacizumab (B), a selective anti-VEGF antibody. We hypothesized that this combination would suppress angiogenesis and tumor growth, and yield clinical benefit in B-naïve EOC pts. Methods: Eligible pts had recurrent EOC, ECOG PS 0-1, good end organ function, and no prior exposure to S or B (NCT00436215). All pts received S 200mg twice daily days 1-5 /wk and B 5mg/kg q 2 weeks in 4 wk cycles. Primary endpoints of response and safety were evaluatedand every other cycle by reassessment imaging and every cycle, respectively. Vascular permeability (Ktrans) was measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and metabolic activity by 18FDG-PET scans performed pretreatment, day 3, and at 6 wks. quality of life (QoL) was assessed at every other cycle. Results: 30pts with B naïve EOC were evaluable for toxicity and 25 for response. Clinical benefit occurred in 22/25 (88%); 6/25 pts had partial responses lasting a median of 15.5 mo (mean 15, range 5-22) and 16/25 pts stabilized disease (median 5 mo; mean 6.8; 4+-18 mo). Therapy related gr 3-4 toxicities included hypertension (47%), thrombosis (13%; DVT [3pts] and PE [1pt]), elevated liver enzymes (7%), anal fissure (3%), headache (3%), and hand-foot syndrome (HFS; 3%). Most gr 3-4 toxicities and gr 2 HFS occurred within the first 4 mo and most other gr2-3 toxicities occurred at 5-18mo (hypertension [7%], anal fissure [3%], headache [7%], elevation of amylase/lipase [7%], DVT [7%]). HFS gr 2 toxicity was common (80%); all others were ≤10%. S dose reduction was due to HFS in 73% of pts with S dose reduction to 200mg daily at median 2 cycles (range 1-7). DCE-MRI and PET were done to evaluate predictive biomarker potential and will be presented; QoL indices and correlative studies are under analysis. Conclusions: S+B yields promising clinical benefit in B-naïve EOC pts, with manageable toxicity. Phase II intermittent dosing of S+B yielded similar clinical benefit compared to our phase I continuous dosing S+B (NCT00098592) experience (88% v 85% [11/13]) in B-naïve EOC. Most gr3/4 toxicities were early and manageable.