FDA OKs Lenvatinib for Unresectable Hepatocellular Carcinoma

The US Food and Drug Administration (FDA) has approved lenvatinib for the treatment of unresectable hepatocellular carcinoma (HCC).

An international, multicenter, randomized, open-label, non-inferiority trial, referred to as the REFLECT trial, which enrolled 954 patients with previously untreated, metastatic, or unresectable HCC served as the basis for the approval. Patients were randomized 1:1 to receive either oral, once-daily lenvatinib (12 mg if they had a baseline weight of ≥60 kg or 8 mg if they had a baseline body weight of <60 kg) or oral, twice-daily sorafenib (400 mg). Patients continued on their treatment regimen until radiological disease progression or unacceptable toxicity was noted.

Lenvatinib was found to be noninferior but not statistically superior to sorafenib when it came to overall survival (OS) (HR 0.92; 95% CI: 0.79, 1.06). In those receiving lenvatinib, the median OS was reported to be 13.6 months, while for those receiving sorafenib, the median OS was 12.3 months.

Furthermore, lenvatinib showed a statistically significant improvement in progression-free survival (PFS) compared with sorafenib. In the lenvatinib arm, the median progression-free survival (PFS) was 7.3 months, while in the in the sorafenib arm, the median PFS was just 3.6 months (HR 0.64; 95% CI: 0.55, 0.75; p<0.001) per modified RECIST for HCC (mRECIST), reflecting findings similar to RECIST 1.1 (response evaluation criteria in solid tumors). The overall response rate was higher for those receiving lenvatinib as compared with those who were given sorafenib (41% vs. 12% per mRECIST and 19% vs. 7% per RECIST 1.1).

In order of frequency, hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea were the most common adverse reactions observed in the patients with HCC who were treated with lenvatinib (≥20%).

Recommended lenvatinib dosages for patients with HCC are 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.