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

Jordi Bruix, Won Young Tak, Antonio Gasbarrini, Armando Santoro, Massimo Colombo, Ho Yeong Lim, Vincenzo Mazzaferro, Reiner Wiest, María Reig, Andrea Wagner, Luigi Bolondi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)3412-3419
Number of pages8
JournalEuropean Journal of Cancer
Issue number16
Publication statusPublished - Nov 2013


  • Hepatocellular carcinoma
  • Receptor kinase inhibition
  • Regorafenib
  • Safety Second line
  • Tolerability

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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