Efficacy and safety of single-agent sunitinib in treating patients with advanced hepatocelluar carcinoma after sorafenib failure: a prospective, open-label, phase II study

Abstract

BACKGROUND: This is an open label and single arm phase II study to assess the efficacy and tolerability of sunitinib for the treatment of sorafenib-refractory advanced hepatocellular carcinoma (HCC) patients. METHODS: Between October, 2008 and October, 2010, eligible patients with advanced HCC and documented disease progression after sorafenib treatment received sunitinib 37.5 mg continuously at Queen Mary Hospital, Hong Kong. Response assessment was performed after every 8 weeks. The primary endpoint was time-to-progression (TTP) and the secondary endpoints were tumor response rate (RR), overall survival (OS) and safety. RESULTS: At the time of analysis, 38 patients were recruited in the trial. The median age was 56 years (range, 27-80) and all patients were in ECOG Performance Status 0-1. Ninety-five percent of patients were chronic hepatitis B carriers with underlying Child-Pugh A and B cirrhosis in 70% and 30% of the enrolled patients, respectively. Ten (25%) patients had tumor vascular invasion and 32 (80%) patients had extra-hepatic metastasis. Among 35 evaluable patients, RR was 6% with 2 patients achieved partial response and another 12 (34%) patients achieved stable disease. Overall, 40% of patients derived clinical benefits from sunitinib treatment for at least 8 weeks. The median TTP was 2.9 months (0.5-15) and OS was 5.2 months (1-22.5). Malaise (60%), neutropenia (45%) and diarrhea (36%) were the most commonly encountered adverse events, with nearly 30% of patients experienced grade 3 or 4 toxicity. No treatment-related death was reported. CONCLUSIONS: Sunitinib has substantial anti-tumour activity with manageable toxicity profile in treating sorafenib-refractory advanced HCC population. These data may imply sunitinib inhibits signaling pathways involved in sorafenib resistance and support the hypothesis of sequential use of antiangiogenic tyrosine kinase inhibitors in treating advanced HCC patients.