Experience with early sorafenib treatment with mTOR inhibitors in hepatocellular carcinoma recurring after liver transplantation

Federica Invernizzi, Massimo Iavarone, Claudio Zavaglia, Stefano Mazza, Umberto Maggi, Lucia Cesarini, Barbara Antonelli, Aldo Airoldi, Matteo Angelo Manini, Angelo Sangiovanni, Giorgio Rossi, Maria Francesca Donato, Luca Saverio Belli, Pietro Lampertico

Research output: Contribution to journalArticle

Abstract

Background. Sorafenib (SOR) is currently used for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT) when HCC is unsuitable for surgical/locoregional treatments. We evaluated safety and effectiveness of early introduction of SOR after HCC-recurrence. Methods. All patients with HCC-recurrence after LT treated with SOR in 2 centers were included (January 2008 to June 2018). Baseline and on-treatment data were collected. Results. Fifty patients early treated with SOR for HCC-recurrence after LT (74% mammalian target of rapamycin inhibitor [mTORi], 54% HCC-treated at baseline) were enrolled. During 7.3 (0.3-88) months of SOR, all patients had at least one adverse event (AE), 56% graded 3-4. SOR was reduced in 68%, being AEs the main cause of reduction, and discontinued in 84% (60% symptomatic progression, 33% AE). Objective response was obtained in 16% and stable disease in 50%. Median time to radiological progression was 6 months (95% confidence Interval [CI], 4-8). Thirty-three patients (69%) died, 94% for HCC progression. Median overall survival (OS) was 18 months (95% CI, 8-27); 5-year OS was 18% (95% CI, 4%-32%). Baseline predictors of OS were SOR+mTORi (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; P = 0.04), previous curative treatments (HR, 0.3; 95% CI, 0.2-0.7; P = 0.003) and alpha-fetoprotein > 100 ng/mL (HR, 2.5; 95% CI, 1.1-5.0, P = 0.02). At multivariate analysis, HCC curative treatment was the only independent predictor (HR, 0.4; 95% CI 0.2-1.0; P = 0.04). Conclusions. Early and combined treatment with SOR and mTORi resulted in a favorable safety profile, while its effectiveness should be confirmed by meta-analysis of previous studies or by larger studies. Curative treatment for HCC resulted the only independent predictor of OS.

Original languageEnglish
Pages (from-to)568-574
Number of pages7
JournalTransplantation
DOIs
Publication statusAccepted/In press - Jan 1 2020

ASJC Scopus subject areas

  • Transplantation

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