Research in context
Evidence before this study
We searched PubMed from inception up to March 16, 2017 using the search terms “phase 3” [Title/Abstract] OR “phase III” [Title/Abstract] AND “hepatocellular carcinoma” [MeSH Terms]. The search was restricted to clinical trials in English language only and yielded 65 reports. Of these publications, 21 described the use of targeted drugs for treatment of hepatocellular carcinoma, 11 were studies of single-drug sorafenib treatment, and three were studies of sorafenib in combination with another drug. Five trials investigated targeted agents following treatment with sorafenib and four trials investigated first-line treatment of hepatocellular carcinoma with sorafenib as the comparator. None of these four trials met their primary endpoints of non-inferiority or superiority over sorafenib in terms of overall survival.
Added value of this study
To our knowledge, this is the first global phase 3 trial in 10 years to meet its primary endpoint of non-inferiority in terms of overall survival against sorafenib as a first-line treatment for hepatocellular carcinoma. Furthermore, lenvatinib showed statistically significant and clinically meaningful improvement in terms of all secondary endpoints (progression-free survival, time to progression, and objective response rate) with a reasonable safety profile.
Implications of all the available evidence
The results of this study support lenvatinib as a first-line treatment option for patients with unresectable hepatocellular carcinoma.