FDA Approves Lenvatinib (Lenvima) for Liver Cancer

Nick Mulcahy


August 16, 2018

The US Food and Drug Administration (FDA) has approved lenvatinib capsules (Lenvima, Eisai) for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

The kinase inhibitor has previously been approved for differentiated thyroid cancer and renal cell cancer.

The safety and efficacy of lenvatinib in HCC are based on the randomized, open-label trial known as REFLECT, which used a noninferiority design involving sorafenib (Nexavar, Bayer), the treatment standard in this setting at the time of the trial, as the comparator.

The REFLECT trial assigned 954 treatment-naive patients with metastatic or unresectable HCC to lenvatinib at 8 mg or 12 mg once per day (n = 478) or sorafenib at 400 mg twice daily (n = 476).

Median overall survival was 13.6 months with lenvatinib compared with 12.3 months with sorafenib. Thus, the trial demonstrated that lenvatinib was noninferior (but not statistically superior) to sorafenib for overall survival, which was the primary endpoint (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.79 - 1.06).

Median progression-free survival was 7.3 months in the lenvatinib group and 3.6 months in the sorafenib group (HR, 0.64; 95% CI, 0.55 - 0.75; P < .001) per modified RECIST [mRECIST] criteria for HCC; findings were similar according to RECIST 1.1.

The overall response rate was higher for the lenvatinib group than the sorafenib group (41% vs 12% per mRECIST and 19% vs 7% per RECIST 1.1).

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

Results from the phase 3 REFLECT study were first presented at the American Society of Clinical Oncology 2017 Annual Meeting, as reported by Medscape Medical News.

At that time, study investigator Ann-Lii Cheng, MD, PhD, from the National Taiwan University Hospital, provided some further context for the results. He explained that HCC is the second leading cause of cancer death worldwide, and, at the time, sorafenib was the only approved systemic therapy proven to extend overall survival in the first-line setting.

"Over the past 10 years, four global phase 3 trials have failed to meet the primary endpoints of noninferiority or superiority to sorafenib in overall survival," he said. That all changed with the REFLECT trial and its positive results.

The recommended lenvatinib dosages for patients with HCC are 12 mg orally once daily in patients with 60 kg or greater actual body weight or 8 mg orally once daily in patients with less than 60 kg actual body weight.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

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