Prolonged tumor response associated with sequential immune checkpoint inhibitor combination treatment and regorafenib in a patient with advanced pretreated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Besides sorafenib, regorafenib and lenvatinib, recent data have shown clinical activity of the PD-1 monoclonal antibody nivolumab. We present the case of a sorafenib-refractory patient probably experiencing progressive disease during immune checkpoint inhibitor combination treatment with the anti-PD-1 monoclonal antibody nivolumab and the anti-GITR monoclonal antibody BMS-986156 within a clinical phase-1 trial followed by a prolonged tumor response according to RECIST v. 1.1 during third-line treatment with the multi-kinase inhibitor regorafenib. Prolonged tumor response may solely be induced by third-line regorafenib monotherapy or may represent late treatment response to combination immunotherapy. Data from this clinical case report support future exploration of combination treatment of the oral multi-kinase inhibitor regorafenib with PD-(L)1 targeted monoclonal antibodies in patients with advanced HCC.