Table 5. Negative results from studies of targeted agents in hepatocellular carcinoma.

Therapy	Study result	Study citation
Brivanib vs. sorafenib	Brivanib did not meet noninferiority criteria and was less well-tolerated	Johnson PJ, et al. J Clin Oncol 2013
Linifanib vs. sorafenib	Linifanib did not meet noninferiority OS boundaries and safety results favored sorafenib	Cainap C, et al. J Clin Oncol 2015
Vandetanib vs. sorafenib	Vandetanib demonstrated limited clinical activity	Hsu C, et al. J Hepatol 2012
Sunitinib	Pronounced toxicities and only modest antitumor activity in HCC	Faivre S, et al. Lancet Oncol 2009;10:794-800; Zhu AX, et al. J Clin Oncol 2009
Sorafenib with erlotinib	Combination did not improve OS	Zhu AX, et al. J Clin Oncol 2015;33:559-566
Sorafenib with tigatuzumab	Sorafenib with tigatuzumab did not improve TTP	Cheng AL, et al. J Hepatol 2015
Everolimus vs. placebo after sorafenib failure	Did not improve OS	Zhu AX, et al. JAMA 2014
Ramucirumab vs. placebo after sorafenib failure	Did not improve OS	Zhu AX, et al. Lancet Oncol 2015
Axitinib vs. placebo after sorafenib failure	Did not improve OS	Kang YK, et al. Ann Oncol 2015

OS, overall survival; HCC, hepatocellular carcinoma; TTP, time to progression.