Efficacy and Safety of Combination Therapy With Everolimus and Sorafenib for Recurrence of Hepatocellular Carcinoma After Liver Transplantation P. De Simone, L. Crocetti, D. Pezzati, I. Bargellini, D. Ghinolfi, P. Carrai, G. Leonardi, C. Della Pina, D. Cioni, L. Pollina, D. Campani, C. Bartolozzi, R. Lencioni, and F. Filipponi ABSTRACT Background. Recurrence of hepatocellular carcinoma (HCC) after liver trans- plantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/ protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. Methods. This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVLþSORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received 1 dose of the study drug. Results. Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVLþSORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL mon- otherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). From the Hepatobiliary Surgery and Liver Transplantation Unit (P.D.S., D.P., D.G., P.C., G.L., F.F.), Radiology Department (L.C., I.B., C.D.P., D.C., C.B., R.L.), and Pathology Department (L.P., D.C.), University of Pisa Medical School Hospital, Pisa, Italy. Address reprint requests to Paolo de Simone, MD, Hep- atobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124 Pisa, Italy. E-mail: p.desimone@ao-pisa.toscana.it ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.10.035 Transplantation Proceedings, 46, 241e244 (2014) 241