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

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 safety and outcomes of regorafenib as second-line treatment for HCC-recurrence after liver transplantation (LT). This is a retrospective, multicentre, 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 1 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 5. Twenty-four patients developed progression (38% extra-hepatic growth, 33% new extra-hepatic 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.