Sorafenib for Patients with Hepatocellular Carcinoma and Child-Pugh B Liver Cirrhosis: Lessons Learned from a Terminated Study.

LESSONS LEARNED: Recruitment of patients with advanced hepatocellular carcinoma and Child-Pugh B for sorafenib treatment and additional pharmacokinetic studies is challenging. Patients with Child-Pugh B liver cirrhosis have high rates of cirrhosis-related adverse events.

BACKGROUND

Few data are available on the pharmacokinetics (PK) of sorafenib in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh B liver cirrhosis. This study aimed to explore the sorafenib PK and its relationship with efficacy and toxicity in these patients.

METHODS

Patients with advanced HCC and Child-Pugh B7-8 liver function were prospectively recruited at a tertiary center. Adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were recorded. Patients received a starting dose of 200 b.i.d. with toxicity-adjusted dose escalation to a target dose of 400 mg b.i.d. with PK sampling at fixed time points.

RESULTS

Between May 2014 and March 2017, 12 patients were screened, of whom 7 progressed to a terminal stage during the screening (n = 6) or shortly after recruitment (n = 1). The five included patients had median PFS of 3.8 months (range, 1.7-10.8) and OS of 7.4 months (range, 1.7-25.8). Three patients had severe AEs and one patient had a partial response with an OS of 25.8 months. In 2017, the trial was aborted for lack of accrual.

CONCLUSION

Because of low accrual, no conclusion can be drawn on the sorafenib PK in patients with advanced HCC and Child-Pugh B liver cirrhosis. The poor survival and frequent cirrhosis-related AEs suggest limited benefit for most of these patients.