On August 16, 2018, the Food and Drug Administration approved lenvatinib capsules (Lenvima, Eisai Inc.) for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).
Approval was based on an international, multicenter, randomized, open-label, non-inferiority trial (REFLECT; NCT01761266) conducted in 954 patients with previously untreated, metastatic or unresectable HCC. Patients were randomized (1:1) to receive lenvatinib (12 mg orally once daily for patients with a baseline body weight of ≥60 kg and 8 mg orally once daily for patients with a baseline body weight of <60 kg) or sorafenib (400 mg orally twice daily). Treatment continued until radiological disease progression or unacceptable toxicity.
REFLECT demonstrated that lenvatinib was non-inferior but not statistically superior to sorafenib for overall survival (OS) (HR 0.92; 95% CI: 0.79, 1.06). Median OS in the lenvatinib arm was 13.6 months and 12.3 months in the sorafenib arm. REFLECT also demonstrated a statistically significant improvement in progression-free survival (PFS) with lenvatinib as compared to sorafenib. Median PFS was 7.3 months in the lenvatinib arm and 3.6 months in the sorafenib arm (HR 0.64; 95% CI: 0.55, 0.75; p<0.001) per modified RECIST for HCC (mRECIST); findings were similar according to RECIST 1.1. The overall response rate was higher for the lenvatinib arm as compared to sorafenib (41% vs. 12% per mRECIST and 19% vs. 7% per RECIST 1.1).
The most common adverse reactions observed in the lenvatinib-treated patients with HCC (≥20%) in order of decreasing frequency were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea.
The recommended lenvatinib dosages for patients with HCC are the following:
- 12 mg orally once daily in patients 60 kg or greater actual body weight or
- 8 mg orally once daily in patients less than 60 kg actual body weight.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
This announcement was originally published on the Food and Drug Administration website on August 16, 2018.