A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib

The SHARP study in 2007 [1] and the Asia Pacific study in 2008 [2] led to the worldwide approval of sorafenib as the standard therapy for unresectable hepatocellular carcinoma (HCC). However, clinical trials investigating sunitinib [3] , brivanib [4] , and linifanib [5] as first-line treatments, with sorafenib as a control arm, failed to meet their primary endpoint of improving overall survival (OS). In addition, global phase III studies investigating secondline therapy with brivanib [6] , everolimus [7] , and ramucirumab [8] , and a regional trial investigating S-1 (tegafur/gimeracil/oteracil) in Japan, were unsuccessful ( Table 1 ). Thus, sorafenib was the only systemic therapeutic agent available for HCC, and for some time no options were available for patients with progressive disease or those intolerant to sorafenib. However, between June 2016 and January 2017, promising results of global phase III studies were reported. The results of a trial of regorafenib were reported at a conference [9] and in a journal [10] , and results with lenvatinib were reported in a press release [11] , indicating the arrival of a new era of liver cancer therapy.