Lenvatinib for treatment of recurrence hepatocellular carcinoma after liver transplantation: A case series

Background and Aims Lenvatinib (Len), an oral inhibitor of multiple receptor tyrosine kinases, is approved as first-line treatment in patients with advanced hepatocellular carcinoma (HCC). Limited data have been published regarding the efficacy and safety of Len in patients with HCC recurrence after liver transplantation (LT). Method Retrospective study including 9 patients with HCC recurrence post-LT treated with Len as first-line regimen. Baseline characteristics and adverse events during treatment were analysed. Progression-free survival and overall survival in the Len group were compared with a historical cohort of patients with HCC recurrence after LT treated with Sorafenib (SOR). Results 8/9 patients were male, with a median age of 60 years. (IQR 56-77). HCC recurrence was both intra and extra-hepatic in 6/9 patients (66%), only extrahepatic in 2 cases (22%) and only intrahepatic in 1 case. Median time from LT to start of Lenvatinib was 4.3 years. Before starting Lenvatinib, 5/9 patients (55%) had already received surgery or locoregional treatment for HCC. The most common adverse events (AEs) were hypertension and fatigue with a single patient experiencing a grade 3 adverse event (proteinuria in the nephrotic range) requiring drug withdrawal. No rejections were observed. Three patients required modification of immunosuppression during the the first 8 weeks of Len treatment. The progression-free survival (PFS) from Len initiation was 321 days. Seven patients experienced disease progression under Len treatment and were shifted to SOR as second-line treatment. A single patient with progressive disease died 2 months after Len withdrawal for tumor progression. When comparing the 9 patients with HCC recurrence treated with LEN, with a balanced cohort of 22 historical patients treated with SOR, LEN was associated with a better progression-free survival (p=0.02) and overall survival (p=0.011) (Fig. 1) Lenvatinib (Len), an oral inhibitor of multiple receptor tyrosine kinases, is approved as first-line treatment in patients with advanced hepatocellular carcinoma (HCC). Limited data have been published regarding the efficacy and safety of Len in patients with HCC recurrence after liver transplantation (LT). Retrospective study including 9 patients with HCC recurrence post-LT treated with Len as first-line regimen. Baseline characteristics and adverse events during treatment were analysed. Progression-free survival and overall survival in the Len group were compared with a historical cohort of patients with HCC recurrence after LT treated with Sorafenib (SOR). 8/9 patients were male, with a median age of 60 years. (IQR 56-77). HCC recurrence was both intra and extra-hepatic in 6/9 patients (66%), only extrahepatic in 2 cases (22%) and only intrahepatic in 1 case. Median time from LT to start of Lenvatinib was 4.3 years. Before starting Lenvatinib, 5/9 patients (55%) had already received surgery or locoregional treatment for HCC. The most common adverse events (AEs) were hypertension and fatigue with a single patient experiencing a grade 3 adverse event (proteinuria in the nephrotic range) requiring drug withdrawal. No rejections were observed. Three patients required modification of immunosuppression during the the first 8 weeks of Len treatment. The progression-free survival (PFS) from Len initiation was 321 days. Seven patients experienced disease progression under Len treatment and were shifted to SOR as second-line treatment. A single patient with progressive disease died 2 months after Len withdrawal for tumor progression. When comparing the 9 patients with HCC recurrence treated with LEN, with a balanced cohort of 22 historical patients treated with SOR, LEN was associated with a better progression-free survival (p=0.02) and overall survival (p=0.011) (Fig. 1)