I read with interest the 2-center experience on sorafenib treatment for recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT).1 The study reports retrospective data on 50 cases, ¾ of whom were treated with mammalian target of rapamycin inhibitor (mTORi), describing a high rate of severe adverse events (grade 3–4 in more than half of the cases). Nevertheless, median overall survival was 18 months, much longer than that historically reported for untreated cases. Although main cause of death was HCC progression (in 94%), 2 cases died because of treatment adverse events. However, authors conclude that combined treatment with sorafenib and mTORi resulted in a favorable safety profile, while its effectiveness should be confirmed by meta-analysis of previous studies or by larger studies.1
Optimal management of HCC recurrence after LT remains a grey area, although sorafenib, despite heterogeneous results in published studies, seems to be an appropriate treatment for HCC recurrence unsuitable for surgery or locoregional treatment.2,3 Moreover, due to the consolidated evidence of both efficacy and safety of sorafenib for HCC in nontransplant setting,4 it would be unethical to perform trials comparing sorafenib versus placebo for HCC recurrence after LT. Anyway, assuming that due to the concern of possible drug interaction in the setting of LT, a theoretical safety issue of sorafenib could exist, neither the present or the past studies, including a systematic review and meta-analysis, could rule it out. In fact, results of a recent meta-analysis of published studies on survival of patients treated with sorafenib for HCC recurrence after LT showed that, after HCC progression, the second cause of death was bleeding, reported only in patients undergoing mTORi therapy.5 Moreover, albeit low quality of included studies (all retrospective) could affect the results, this meta-analysis reports data on the biggest sample of cases treated with sorafenib for HCC recurrence after LT, reinforcing the previously suggested concern about safety with the combination of sorafenib and mTORi.
In conclusion, further studies are needed to evaluate the optimal management of HCC recurrence after LT. Sorafenib is actually first-line treatment for advanced HCC recurrence after LT. However, safety profile, in particular when sorafenib is associated with mTORi, would need further evidence.
1. Invernizzi F, Iavarone M, Zavaglia C, et al. Experience with early sorafenib treatment with mTOR inhibitors in hepatocellular carcinoma recurring after liver transplantation. Transplantation. 2020; 104:568–574
2. Mancuso A, Perricone G. Hepatocellular carcinoma and liver transplantation: state of the art. J Clin Transl Hepatol. 2014; 2:176–181
3. Mancuso A, Mazzarelli C, Perricone G, et al. Sorafenib efficacy for treatment of HCC recurrence after liver transplantation is an open issue. J Hepatol. 2014; 60:681
4. Zavaglia C, Airoldi A, Mancuso A, et al. Adverse events affect sorafenib efficacy in patients with recurrent hepatocellular carcinoma after liver transplantation: experience at a single center and review of the literature. Eur J Gastroenterol Hepatol. 2013; 25:180–186
5. Mancuso A, Mazzola A, Cabibbo G, et al. Survival of patients treated with sorafenib for hepatocellular carcinoma recurrence after liver transplantation: a systematic review and meta-analysis. Dig Liver Dis. 2015; 47:324–330