SourceGastrointestinal Cancer Unit, 12 October University Hospital, Madrid, Spain. cgomezm@cnio.es.

There is currently no consensus on the most suitable treatment for hepatocellular carcinoma (HCC) recurrence following liver transplant. This open, multicenter, retrospective, noncontrolled cohort study aimed to evaluate the safety and preliminary efficacy of the combined use of an mTOR inhibitor and sorafenib in this setting. It included 31 patients with post-liver transplant HCC recurrence after which the immunosuppressive therapy was changed to mTOR inhibitors, and systemic treatment with sorafenib was initiated.

The combination was maintained until symptomatic tumor progression, death, hepatic decompensation or unacceptable toxicity. Primary treatment efficacy was determined by overall survival and progression-free survival and, secondary efficacy by overall response rate. Toxicity parameters associated with the use of sorafenib and mTOR inhibitors were also analyzed. The overall response rate according to RECIST criteria was 3.8%, with sustained stabilization of the disease (clinical benefit rate) in 13 additional cases (50%). The median overall survival was 19.3 months (CI 95% 13.5-25.2) and the median time to progression was 6.8 months (CI 95% 2.3-11.2). Only 2 cases of hyperglycemia and 1 of grade 3-4 mucositis were reported, possibly related to mTOR inhibitors.

The most common severe side effect probably related to sorafenib was diarrhea (16%). It was concluded that the co-administration of sorafenib and an mTOR inhibitor could be effective despite notable toxicity in patients with HCC recurrence after liver transplant not suitable for radical therapy. The toxicity and efficacy of this combination needs to be further evaluated in randomized controlled studies to be considered a valid option.