Molecular Targeted Agents for Hepatocellular Carcinoma: Current Status and Future Perspectives

Proposal of Primary Endpoints for TACE Combination Trials with Systemic Therapy: Lessons Learned from 5 Negative Trials and the Positive TACTICS Trial

“…Both the TACE-specific PFS measure we proposed in the TACTICS trial and TTTP are suitable surrogate endpoints for OS. Therefore, either TACE-specific PFS or TTTP may be a useful surrogate endpoint to OS even in registration trials by pharmaceutical companies which combine systemic therapy [21, 22] and TACE.…”

Pembrolizumab for the Treatment of Hepatocellular Carcinoma

“…The exclusion criterion is tumor infiltration of the main portal vein (Vp4) or inferior vena cava [21]. Positive results of this phase III trial would lead to the worldwide approval of pembrolizumab as a promising treatment option in addition to conventional molecular-targeted agents [22, 23]. However, striking news released by Merck on February 19, 2017 indicate that this trial did not meet its primary endpoint of prolonging PFS or OS compared with placebo plus best supportive care [24].…”

Lenvatinib in Advanced Hepatocellular Carcinoma

“…Since then, other molecular-targeted agents superior to sorafenib in efficacy or safety in the first-line treatment of HCC were developed and tested in clinical trials (Table 1) [3]. However, a superiority trial of sunitinib [4] and noninferiority followed by superiority studies of brivanib or linifanib versus sorafenib [5,6] were reported as negative; a superiority trial of sorafenib plus erlotinib versus sorafenib was also unsuccessful [7].…”