Lenvatinib as first-line therapy for recurrent hepatocellular carcinoma after liver transplantation: Is the current evidence applicable to these patients?

Abstract

Liver transplantation (LT) is one of the leading curative therapies for hepatocellular carcinoma (HCC). Despite recent optimization of transplant selection criteria, including alpha-feto protein, HCC recurrence after LT is still the leading cause of death in these patients. During the last decades, effective systemic treatments for HCC, including tyrosine kinase inhibitors and immunotherapy, have been approved. We describe the clinical scenario of a patient with recurrence of HCC five years after LT, who received lenvatinib as first-line systemic therapy to introduce systemic treatment options in this clinical setting. In this opinion review, we detail first and second-line systemic treatment options, focusing on those feasible for patients with recurrent HCC after LT. Several trials have evaluated new drugs to treat HCC patients in first and second-line therapy, but patients with recurrent HCC after LT have been excluded from these trials. Consequently, most of the evidence comes from observational retrospective studies. Whether tyrosine kinase inhibitors will remain the primary therapeutic approach in these patients, due to a relative contraindication for immunotherapy, may be clarified in the near future.

Keywords: Liver transplantation; Recurrence; Systemic therapies; Hepatocellular carcinoma

Core Tip: Post-transplant hepatocellular carcinoma (HCC) recurrence is a significant negative predictor of survival. There is no consensus on the treatment of recurrence. If possible, resection should be attempted. The use of systemic chemotherapy after transplant is limited to small retrospective cohort studies. Immunotherapy with checkpoint inhibitors in the post-transplant setting is challenging due to the potentially increased risk of allograft rejection. This opinion review illustrates a late post-transplant HCC recurrence treated with lenvatinib, with good tolerance and overall survival after lung and adrenal metastasis resections in a patient previously intolerant to sorafenib.