A case of complete remission with durvalumab-cabozantinib sequential therapy for advanced hepatocellular carcinoma

Cabozantinib, a tyrosine kinase inhibitor that targets not only vascular endothelial growth factor receptors but also hepatocyte growth factor receptor, is characteristically administered as a second or greater line treatment for unresectable hepatocellular carcinoma. Complete remission are extremely rare. We here report a dramatic response to cabozantinib as later-line therapy in a 57-year-old woman with advanced hepatocellular carcinoma. She was found to have multiple recurrences in the remnant liver and bilateral lung metastases 4 months after hepatectomy. Retrospective immunohistochemical staining of the resected specimen for hepatocyte growth factor receptor revealed weak positivity. Her disease was judged to be hyper-progressive after 2 months of treatment with atezolizumab plus bevacizumab. Second-line treatment with lenvatinib achieved a temporary reduction in alpha-fetoprotein concentration; however, her disease progressed. One week after administering a single dose of durvalumab, 20 mg of cabozantinib once daily was initiated. Subsequently, her alpha-fetoprotein concentrations decreased markedly, normalizing at 12 weeks, and computed tomography revealed only minor scar-like micronodules in the lungs. She continued cabozantinib, requiring two dose reductions because of adverse effects at 4 and 26 weeks. Cabozantinib was discontinued 11 months after commencing it. She has now remained drug- and cancer-free for 12 months.