Lenvatinib Approved by FDA for Unresectable Hepatocellular Carcinoma

Officials with the FDA have 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, noninferiority 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 noninferior 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 effects observed in the patients with HCC treated with lenvatinibin (≥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.

Reference

FDA approves lenvatinib for unresectable hepatocellular carcinoma [news release]. Silver Spring, MD; August 16, 2018: FDA website. http://www.pharmacytimes.com/link/206. Accessed August 16, 2018.