Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumor: A phase II study of the Spanish Neuroendocrine Tumor Group (GETNE0801).

Abstract

4113 Background: Sorafenib (S) and bevacizumab (B) as single agents have shown efficacy in NETs phase II trials. S+B combination has shown manageable toxicity in phase I trials in solid tumors. The aim of this study was to evaluate the efficacy and toxicity of the STI's combination in NETs. Methods: Phase II, controled clinical trial, carried out in 10 centers in Spain. Eligibility criteria: measurable, non-resectable, histologically confirmed moderately or well-differentiated NETs; 1 prior chemotherapy treatment allowed; ECOG PS 0–2. Duration of treatment: 6 months. Pts received S 200 mg bid (days 1 to 5 of each week) and B 5mg/Kg once every 2 weeks (day 1 of week 1). Efficacy results were calculated with intention to treat sample (n=41). Results: 44 pts were enrolled, 59.1% men. Median age was 60 years (range 32–76) and ECOG PS was 1 for 54.5% of pts. Carcinoid tumors: 31 pts and islet cell carcinoma (ICC): 13 pts were evaluated. Histology grade was well-differentiated in 95.5% of pts. Target lesions of pts at baseline were mainly in the liver (86.4%) and lymphatic nodes (31.8%). ORR (RECIST 1.1) was 9.8% and DCR 95.1%. PR was documented in 3 pts with carcinoid tumors and 1 PR with ICC. Estimated PFS was a median of 12.4 months (95%CI: 9.4-16.2) and a PFS rate at 6 months of 90.9% (30/33). A total of 8 pts finished the study prematurely: 6 due to adverse events and 2 due to consent withdraw. Most common grade 3-4 toxicities were hand-foot syndrome (20.5%) and asthenia (15.9%). No major response was observed with Chromogranin/5-HIAA analysis. Conclusions: This is the first study of targeted STI's combination in advanced NETs. The final results of the combination of low-dose sorafenib + bevacizumab showed a potential clinical benefit, albeit with moderate toxicities. Further studies should be confirm the real value of the targeted combination therapies in this setting, according to International Consensus Report (Kulke M, et al; JCO published online on January 24, 2011).