Long‐term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion

Lenvatinib is a novel multikinase inhibitor that has recently shown antitumor activity against hepatocellular carcinoma (HCC) in a phase III trial. We report the case of a woman in whom lenvatinib showed long‐term antitumor activity, and in whom computed tomography (CT) scans revealed a series of suggestive radiological changes on the intratumor vascularity. A 68‐year‐old woman with hepatitis C virus‐related liver disease presented with multiple HCCs. Following previous therapy, including six sessions of transcatheter arterial chemoembolization, we introduced lenvatinib monotherapy. Lenvatinib could rapidly cause hypovascularity in the main hypervascular target lesion, and portal vein tumor thrombosis also became undetectable 11 months after the initiation of lenvatinib. These radiological changes suggested that lenvatinib could exert not only anti‐angiogenic activity but also direct antitumoral effect. Of note, CT scans during lenvatinib treatment revealed the target lesion as a low‐density area in the early arterial phase, whereas scans during drug interruption due to proteinuria showed that the lesion was enhanced in the arterial phase. Finally, near‐complete response could be achieved as the best response. We successfully managed various adverse events including proteinuria and hypertension, and the patient was able to continue this lenvatinib therapy for more than 4 years with well‐controlled general condition. We report the first case of a patient with HCC in whom lenvatinib monotherapy demonstrated long‐term antitumor activity. Suggestive radiological changes reflecting intratumor vascularity as presented here should be considered in patients receiving lenvatinib for HCC.