FDA Accepts sNDA for Lenvatinib for the Treatment of Hepatocellular Carcinoma


On September 26, Eisai Inc announced the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental New Drug Application (sNDA) for lenvatinib  (Lenvima) for potential use in the first-line treatment of patients with hepatocellular carcinoma.

“Patients with advanced liver cancer face a debilitating, life-threatening disease and additional treatment options are needed for these patients,” said Kenichi Nomoto, PhD, Chief Scientific Officer, Oncology Business Group, Eisai. “Given the importance of the REFLECT study results, in which lenvatinib was the first first-line systemic therapy to demonstrate positive results when compared to sorafenib in a phase III trial in patients with hepatocellular carcinoma in more than a decade, we will work closely with the FDA in hopes of bringing a new treatment option to patients living with advanced liver cancer.”


The sNDA submission is based on the positive results of the phase III REFLECT trial. In this study, lenvatinib demonstrated a treatment effect on overall survival by statistical confirmation of noninferiority to sorafenib. This is the first positive phase III study of a systemic treatment in comparison to sorafenib (Nexavar) in this patient population. Additionally, patients experienced statistically significant and clinically meaningful improvements in the secondary efficacy endpoints of progression-free survival, time to progression, and objective response rate.

REFLECT was an international, multicenter, open-label, randomized, noninferiority phase III study to compare the efficacy and safety of lenvatinib vs sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma. Patients (N = 954) at 183 trial sites in 21 countries were randomized to receive lenvatinib at 12 mg or 8 mg once a day depending on body weight (≥ 60 kg or < 60 kg; n = 478) or sorafenib at 400 mg twice a day (n = 476).

Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival. The secondary efficacy endpoints of this study were progression-free survival, time to progression, and objective response rate.

The median overall survival for patients treated with lenvatinib was 13.6 months compared to 12.3 months for sorafenib (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = 0.79–1.06). Median progression-free survival was 7.4 months with lenvatinib with a median time to progression of 8.9 months compared to a median progression-free survival of 3.7 months (HR = 0.66, 95% CI = 0.57–0.77; P < .00001) and median time to progression of 3.7 months on sorafenib (HR = 0.63, 95% CI = 0.53– 0.73; P < .00001). In addition, lenvatinib demonstrated a significantly higher objective response rate (24%) compared to sorafenib (9%; odds ratio = 3.13, 95% CI = 2.15–4.56; P < .00001). Endpoints were evaluated using modified Response Evaluation Criteria in Solid Tumors and determined by investigator assessment. Independent radiologic review is now complete.

Safety Profiles

In this study, the most common treatment-emergent adverse events observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, decreased weight, and fatigue. In the sorafenib arm, the most common treatment-emergent adverse events were palmar-plantar erythrodysesthesia, diarrhea, hypertension, and decreased appetite. Patients who received lenvatinib had fewer instances of palmar-plantar erythrodysesthesia, diarrhea, and alopecia and more instances of hypertension, proteinuria, dysphonia, and hypothyroidism than did patients who received sorafenib.

Nine percent of patients treated with lenvatinib and 7% of patients treated with sorafenib discontinued treatment due to treatment-related adverse events. Forty-three percent of patients treated with lenvatinib and 30% of patients who received sorafenib experienced serious treatment-emergent adverse events.

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®.