First-Line Lenvatinib vs Sorafenib in Unresectable Hepatocellular Carcinoma


Key Points

  • Lenvatinib was noninferior to sorafenib in overall survival; superiority was not achieved.
  • Progression-free survival was longer with lenvatinib. 

In a phase III noninferiority trial reported in The Lancet, Kudo et al found that first-line lenvatinib was noninferior to sorafenib in overall survival of patients with unresectable hepatocellular carcinoma.

Study Details

In the open-label trial, 954 patients from 154 sites in 20 countries in the Asia-Pacific, European, and North American regions were randomized between March 2013 and July 2015 to receive lenvatinib at 12 mg/d for body weight ≥ 60 kg or 8 mg/d for body weight < 60 kg (n = 478) or sorafenib at 400 mg twice daily (n = 476) in 28-day cycles. Randomization was stratified by region, macroscopic portal vein invasion, extrahepatic spread, Eastern Cooperative Oncology Group performance status, and body weight.

The primary endpoint was overall survival in the intent-to-treat population. Noninferiority was achieved if the upper limit of the two-sided 95% confidence interval (CI) for the hazard ratio (HR) for lenvatinib vs sorafenib was < 1.08.

Survival Data

Median follow-up was 27.7 months in the lenvatinib group and 27.2 months in the sorafenib group. Median overall survival was 13.6 vs 12.3 months (HR = 0.92, 95% CI = 0.79–1.06), with the criterion for noninferiority thus being met. Median progression-free survival was 7.4 months vs 3.7 months (HR = 0.66, P <.0001). In total, 33% of patients in the lenvatinib group and 39% in the sorafenib group received anticancer treatment after the study therapy.

Adverse Events

The most common adverse events of any grade were hypertension (42%), diarrhea (39%), decreased appetite (34%), and decreased weight (31%) in the lenvatinib group and palmar-plantar erythrodysesthesia (52%), diarrhea (46%), hypertension (30%), and decreased appetite (27%) in the sorafenib group. Treatment-related adverse events of grade ≥ 3 occurred in 57% vs 49% of patients. Treatment-related serious adverse events occurred in 18% vs 10%, and treatment-related adverse events led to treatment discontinuation in 9% vs 7% in the lenvatinib and sorafenib groups, respectively.

The investigators concluded, “Lenvatinib was noninferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma. The safety and tolerability profiles of lenvatinib were consistent with those previously observed.”

The study was funded by Eisai Inc.

Masatoshi Kudo, MD, of Kindai University Faculty of Medicine, Osaka, is the corresponding author for The Lancet article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.