Use of sorafenib in recurrent hepatocellular carcinoma (HCC) after liver transplantation

Abstract

BACKGROUND: Sorafenib (Sor) is the only approved systemic therapy for advanced HCC yet the safety and efficacy for its use in patients (pts) who developed recurrence after liver transplantation (LT) has not been established. There is an unmet need for treatment option in this group of pts. METHODS: This is a retrospective analysis of pts treated with Sor for recurrent HCC post-LT in Queen Mary Hospital, Hong Kong. RESULTS: During year Jan 2008 to Feb 2014, 25 post-LT pts with HCC recurrence were treated with Sor. Tacrolimus and sirolimus were the immunosuppressant of choice during the same treatment period in 76% (19/25) and 40% (10/25) pts respectively. All pts had Child-Pugh A liver function and ECOG performance status 0-1. Majority of pts were chronic hepatitis B carriers (88%) and male (88%). Median time to recurrence was 13.2 months (range 3.4-71.1). Intrahepatic recurrence and extrahepatic recurrence were found in 52% and 80% of pts respectively. Up to 68% of pts received the standard dose of 800 mg/day. The most common adverse events (AEs) were hand-foot syndrome (44%) and diarrhea (28%). G3 transaminase elevation was found in 4 pts (16%), in which 2 had histological evidence of acute graft rejection. Both cases were associated with tailing down of tacrolimus upon tumor progression, and the liver function recovered after adjustment of immunosuppressant. Nine pts (36%) required dose adjustment. The median maintenance dose was 400 mg/day. The median duration of treatment was 4.44 months (95% CI 2.53-6.44). Median time to progression was 6.21 months (95% CI 2.83-9.63). Median overall survival was 13.6 months (95% CI 7.69-19.61). Ten (40%) pts also received other subsequent systemic therapy. CONCLUSIONS: Sor given in combination with tacrolimus and sirolimus did not lead to unexpected graft rejection. The drug is in general tolerated in this population and toxicities appeared to be similar to non-transplant pts. Further study is required to evaluate for drug interaction and efficacy.