Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre, open-label, phase II safety study

Purpose: We assessed the safety of the multikinase inhibitor regorafenib in patients with hepatocellular carcinoma (HCC) that had progressed following first-line sorafenib. Patients and methods: Thirty-six patients with Barcelona Clinic Liver Cancer stage B or C HCC and preserved to mildly impaired liver function (Child-Pugh class A) received regorafenib 160 mg once daily in cycles of 3 weeks on/1 week off treatment until disease progression, unacceptable toxicity, death or patient/physician decision to discontinue. The primary end-point was safety; secondary end-points included efficacy (including time to progression and overall survival). Results: The median treatment duration was 19.5 weeks (range 2-103). At data cutoff, three patients remained on treatment. Reasons for discontinuation were adverse events (n = 20), disease progression (n = 10), consent withdrawal (n = 2) and death (n = 1). Seventeen patients required dose reductions (mostly for adverse events [n = 15]); 35 patients had treatment interruption (mostly for adverse events [n = 32] or patient error [n = 11]). The most frequent treatment-related adverse events were hand-foot skin reaction (any grade n = 19; grade >= 3 n = 5), diarrhoea (n = 19; n = 2), fatigue (n = 19; n = 6), hypothyroidism (n = 15; n = 0), anorexia (n = 13; n = 0), hypertension (n = 13; n = 1), nausea (n = 12; n = 0) and voice changes (n = 10; n = 0). Disease control was achieved in 26 patients (partial response n = 1; stable disease n = 25). Median time to progression was 4.3 months. Median overall survival was 13.8 months. Conclusion: Regorafenib had acceptable tolerability and evidence of antitumour activity in patients with intermediate or advanced HCC that progressed following first-line sorafenib. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.