Extremely High Objective Response Rate of Lenvatinib: Its Clinical Relevance and Changing the Treatment Paradigm in Hepatocellular Carcinoma

The results of a clinical trial of lenvatinib were published in the Lancet earlier this year [1]. According to the results, the response rate was higher for lenvatinib than for any other known molecular targeted agents in hepatocellular carcinoma (HCC) patients. The response rates based on independent imaging review and investigator review according to the modified RECIST (mRECIST) assessment were extremely high at 40.6 and 24.1%, respectively. The response rate based on independent imaging review according to RECIST 1.1 was also high (18.8%) (Table ​(Table1).1). The response to locoregional treatment (e.g., transcatheter arterial chemoembolization [TACE] and ablation) is correlated with overall survival (OS). In a meta-analysis of seven studies, Vincenzi et al. [2] showed that the hazard ratio (HR) for OS was 0.39 (95% confidence interval [CI] 0.26–0.61, p < 0.0001) when comparing responders and nonresponders among 1,352 patients treated with TACE (n = 1,236), cryoablation (n = 64), and bland transarterial embolization (n = 57). This excellent HR indicated the correlation between response to locoregional therapy and OS benefit (Fig. ​(Fig.1).1). It is established evidence that OS benefit is more prominent in responders to locoregional therapy than in nonresponders evaluated by mRECIST; thus, the evidence that objective response measured by mRECIST predicts survival in patients receiving locoregional therapies is currently recommended in the EASL guidelines [3]. Regarding molecular targeted agents, most sorafenib-treated patients show stable disease, demonstrating the survival benefit of sorafenib treatment. However, the association between response to molecular targeted agents and improved survival remains unclear. This article reviews recent reports based on retrospective studies and prospective clinical trials of molecular targeted agents with an emphasis on the relationship between response to these agents and improvement of patient survival. Open in a separate window Fig. 1. Correlation between objective response and improved OS in early- or intermediate-stage HCC (from Vincenzi et al. [2]).