Lenvatinib Receives FDA Approval for Inoperable Stage 4 Liver Cancer Treatment

On 16 August 2018, the US Food and Drug Administration (FDA) approved lenvatinib capsules (brand name Lenvima) for first-line treatment of patients with unresectable hepatocellular carcinoma (liver cancer).

The approval is based on a study in previously untreated, metastatic or inoperable liver cancer involving 954 patients, the international, multicenter, randomized, open-label REFLECT clinical trial as supporting evidence. This is a non-inferiority study; it tests whether the new drug is as effective as standard treatment.

Patients were randomized at a 1:1 ratio into 2 groups for lenvatinib treatment;

• Experimental arm: patients with initial body weight < 60 kg received 8 mg once daily, and patients weighing > 60 kg received 1 daily 12 mg capsule 8 mg,
• Control arm: sorafenib (brand name Nexavar) was given orally at 400 mg twice daily.

Treatments continued until radiologically demonstrated disease progression or unacceptable adverse effects.

Results

• The REFLECT trial showed lenvatinib to be as effective as sorafenib, but not statistically superior to sorafenib for overall survival.
• Median overall survival was 13.6 months in the lenvatinib arm and 12.3 months in the sorafenib arm.
• For progression-free survival (the time treatment keeps disease controlled), lenvatinib was statistically superior to sorafenib: median progression-free survival was 7.3 months in the lenvatinib arm and 3.6 months in the sorafenib arm.
• Overall response rates were higher with lenvatinib than sorafenib (%41 versus %25 using liver cancer-specific modified RECIST, and with standard RECIST 1.1, %19 versus %7).

The most common (≥% 20) among lenvatinib-treated liver cancer patients' adverse effects were hypertension, fatigue, diarrhea, decreased appetite, arthralgia / myalgia, weight loss, abdominal pain, palmar-plantar erythrodysesthesia (hand and foot rash) syndrome, proteinuria (protein leakage in urine), dysphonia (hoarseness), hemorrhagic events (bleeding), hypothyroidism and nauseaas reported.

For treating hepatocellular carcinoma (liver cancer), recommended lenvatinib dosages are:

• For 60 kg and above, 12 mg once daily,
• For patients below 60 kg, an 8 mg capsule once daily with water.

Lenvatinib acts on the cell membrane's tyrosine kinase receptor as the named receptor by blocking its activity. Tyrosine kinase receptors generally function in cancer cell growth, proliferation, new blood vessel formation and spread to distant tissues.

Lenvatinib has directly entered first-line liver cancer treatment. Remembering the earlier approval in liver cancer of the immunotherapy nivolumab, we can say options have substantially increased for advanced liver cancer, which is very difficult to treat. We will follow and share lenvatinib's approval process in our country.

Note: Lenvatinib previously received approval for thyroid cancer in 2015 and kidney cancer in 2016 from the FDA.

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