Randomised phase II study of docetaxel plus vandetanib versus docetaxel followed by vandetanib in patients with persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: SWOG S0904

Background: Vandetanib is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET, which has demonstrated clinical activity as a single agent and in combination with taxanes. We explored the efficacy, safety and toxicity of docetaxel and vandetanib in women with recurrent ovarian cancer (OC). Methods: Women with refractory or progressive OC were randomised 1: 1 to docetaxel (75 mg/m(2), IV) + vandetanib (100 mg daily, PO, D + V) or docetaxel (75 mg/m(2), D). Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents (as primary therapy) were allowed. The primary end-point was progression free survival (PFS). The study had 84% power to detect a PFS hazard ratio of 0.65, using a one-sided P of 0.1. This corresponds to an increase in median PFS from 3.6 months to 5.6 months. Patients progressing on D were allowed to receive single agent vandetanib (D -> V). Results: 131 Patients were enrolled; two were excluded. 16% had received prior anti-angiogenic therapy. The median PFS estimates were 3.0 mos (D + V) versus 3.5 (D); HR: 0.99 (80% CI: 0.79-1.26). 61 Patients on D + V were assessable for toxicity; 20(33%) had treatment- related Grade (G) 4 events, primarily haematologic. Similarly, 17 (27%) of 64 patients receiving D had G4 events, primarily haematologic. 27 Evaluable patients crossed-over to V. 1/27(4%) experienced a G4 event. G3 diarrhoea was observed in 4% D ! V patients. Median OS was 14 mos (D + V) versus 18 mos (D -> V); HR(OS): 1.25 (80% CI: 0.931.68). Crossover vandetanib response was 4% (1/27 evaluable patients). High plasma IL-8 levels were associated with response to D + V. Conclusions: Combination docetaxel + vandetanib did not prolong PFS relative to docetaxel alone in OC patients. No unexpected safety issues were identified. (C) 2014 Elsevier Ltd. All rights reserved.