Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

Am J Transplant. 2019 Nov;19(11):3176-3184. doi: 10.1111/ajt.15551. Epub 2019 Sep 3.

Abstract

Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; median time on sorafenib was 11.3 (0.7-76.4) months and 14 (1-591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty-four patients developed progression (38% extrahepatic growth, 33% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95% CI, 6.7-19.1) and 38.4 months (95% CI, 18.5-58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision-making in sorafenib-tolerant patients with HCC recurrence after LT.

Keywords: cancer/malignancy/neoplasia; chemotherapy; clinical research/practice; drug interaction; liver transplantation/hepatology; pharmacology; side effects.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery*
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery*
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / etiology
  • Neoplasm Recurrence, Local / pathology
  • Phenylurea Compounds / administration & dosage
  • Prognosis
  • Pyridines / administration & dosage
  • Retrospective Studies
  • Sorafenib / administration & dosage
  • Young Adult

Substances

  • Phenylurea Compounds
  • Pyridines
  • regorafenib
  • Sorafenib