BIOSHARE multicenter neoadjuvant phase 2 study: Results of pre-operative sorafenib in patients with resectable hepatocellular carcinoma (HCC)—From GERCOR IRC.

Abstract

252 Background: This open-label, multicenter, phase II study aimed at investigating the activity of sorafenib including radiological, pathological and biological changes in tumor from patients with resectable HCC. Methods: Preoperative administration of sorafenib 400 mg bid for 4 weeks was followed by surgery. Primary endpoints were antitumor activity and histological changes on paired tumor samples and plasma biomarkers between baseline and post sorafenib. Secondary endpoints were safety, R0 surgery and post-surgical complications. Results: Among 30 patients enrolled, 28 were evaluable for safety. Neoadjuvant sorafenib was not feasible in 3 patients (early limiting toxicities). Twenty-five patients (21 men; median age: 61.5 years) were evaluable for the primary endpoints. Baseline median tumor size was 37 mm and 21 patients (84%) had a single lesion. Median duration and dosing of sorafenib were 28 days and 793 mg/day respectively. Overall, the safety profile of preoperative sorafenib was good. According to RECIST criteria, all patients showed stable disease. Among 19 patients evaluated according to mRECIST and Choi criteria, objective responses were observed for 6 (32%) and 10 (53%) patients respectively. All evaluable patients went on liver resection and no unexpected complication occurred. R0 tumor resection was achieved in 22 patients (88%). Surgical specimen showed macrovascular and microvascular invasion in 12% and 48%, respectively. Intratumor necrosis was observed in 17 (68%) surgical specimen with necrosis ≥ 50% in 24 % of cases. Blood biomarkers analysis showed a trend toward increased angiogenesis biomarkers (VEGF-A, VEGF-C and PlGF) after sorafenib treatment. Biomarkers from pre- and post-treatment tissue will be presented during the meeting. Conclusions: Neoadjuvant sorafenib displays a favorable toxicity profile and yields significant activity in patients with resectable HCC. BIOSHARE trial also allows exploration of drug effects on tumor biology. Clinical trial information: NCT01182272.