A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma.

ABSTRACT

OBJECTIVES: Sorafenib, an oral multikinase inhibitor of the VEGFR/PDGFR/Raf/MEK/ERK pathway, has shown potential activity in patients with recurrent ovarian cancer (OC). One strategy to prolong disease control and survival in patients with OC is maintenance therapy after achieving a complete response. A double-blind, randomized, placebo-controlled, phase II study to assess the efficacy and safety of maintenance therapy with sorafenib in the treatment of OC is presented. METHODS: Patients with epithelial OC or primary peritoneal cancer in complete remission were randomized to sorafenib 400mg BID or matching placebo. The primary endpoint was progression-free survival (PFS). RESULTS: Of 246 randomized patients, 93% had OC; baseline characteristics were balanced between treatment arms. There was no significant difference between sorafenib and placebo arms for PFS (median 12.7 vs 15.7 months; hazard ratio 1.09; 95% CI 0.72-1.63), although there was a notable imbalance in early censoring. The most common ≥ grade 3 adverse events (AEs) were hand-foot skin reaction (39.0% vs 0.8%) and rash (14.6% vs 0%). More patients receiving sorafenib versus placebo required dose reductions (67.5% vs 30.1%), resulting in a lower than planned median daily dose (median 584.6 vs 800.0mg). Treatment with sorafenib was of shorter duration (median 17.6 vs 51.9 weeks) with more frequent discontinuations due to AEs (37.4% vs 6.5%). CONCLUSIONS: Sorafenib 400mg BID cannot be recommended as maintenance therapy for patients with OC in complete remission. Assessment of efficacy was limited by the high rate of dose reductions and early discontinuations.