Lenvatinib is approved to be used alone as the first treatment for a type of liver cancer called hepatocellular carcinoma (HCC) when it cannot be removed by surgery. “First-line treatments”, such as surgery, radiation or drug treatments, are options that might be tried as your first therapy for cancer.

Based on the National Comprehensive Cancer Network (NCCN) 2020 patient guidelines for liver cancer treatment, the preferred first-line drug therapy options for liver cancer include:

• lenvatinib (Lenvima)
• sorafenib (Nexavar)
• atezolizumab (Tecentriq) with bevacizumab (Avastin)

Study: Lenvatinib vs sorafenib in inoperable liver cancer

The REFLECT study, conducted by the manufacturer of lenvatinib, compared it to sorafenib treatment, another first-line drug therapy, in 954 patients with previously untreated and inoperable hepatocellular carcinoma (HCC).

Study results showed that lenvatinib was found to be no worse than (non-inferior to) treatment with sorafenib (another first-line drug used for liver cancer that can’t be removed with surgery). In other words, lenvatinib did not show an improvement in survival (how long patients lived) when statistically compared to sorafenib.

• Patients treated with lenvatinib experienced a median overall survival (OS) of 13.6 months compared to 12.3 months with sorafenib.
• Overall survival is the time from the start of the study to death from any cause and is considered a direct measure of clinical benefit to a patient.
• This was the primary endpoint of the study, or the main endpoint that the study was designed around.

In addition, the time that patients lived without their disease getting worse (median progression-free survival or PFS) was doubled with lenvatinib (7.3 months) compared to sorafenib (3.6 months). This equates to a 36% reduction in risk of disease progression or death.

Lenvatinib also showed nearly 3.5 times the overall response rate (ORR) of sorafenib: 41% (range or CI: 36% to 45%) for lenvatinib vs. 12% (range or CI: 10% to 16%) for sorafenib. ORR is the percent of patients whose tumor is destroyed or reduced in size by a drug. The ORR is composed of the complete response (CR) and the partial response (PR) rates. Improvement in numbers shows that the drug is working.

• The complete response (CR) was 2.1% for lenvatinib and 0.8% for sorafenib. Patients with a complete response have no detectable evidence of a tumor over a specified time period.
• The partial response was 38.5% for lenvatinib and 11.6% for sorafenib. Patients with a partial have a decrease in tumor size over a specified time period.

What kind of side effects occurred with lenvatinib and sorafenib?

Side effects of drug treatment are important to consider when looking at treatment options for cancer treatment

Side effects led to a dose reduction or interruption in treatment in 62% of patients receiving lenvatinib, and led to lenvatinib treatment discontinuation in 20% of patients.

More serious side effects (grade 3-4) in patients being treated for HCC in either treatment arm:

• High blood pressure (hypertension): 24% lenvatinib and 15% sorafenib
• Decreased weight: 8% lenvatinib and 3% sorafenib
• Fatigue: 7% lenvatinib and 6% sorafenib
• Protein in the urine (proteinuria): 6% lenvatinib and 2% sorafenib
• Decreased appetite: 5% lenvatinib and 1% sorafenib
• Hand-foot syndrome skin reaction (palmar-plantar erythrodysesthesia syndrome): 3% lenvatinib and 11% sorafenib

Common side effects (at least 20%) with lenvatinib in patients being treated for liver cancer overall:

• Hypertension
• Fatigue
• Diarrhea
• Decreased appetite
• Arthralgia/myalgia (joint/muscle pain)
• Decreased weight
• Abdominal (stomach area)pain
• Palmar-plantar erythrodysesthesia syndrome (skin reaction on hand and feet)
• Proteinuria
• Dysphonia (difficulty in speaking)
• Hemorrhagic (bleeding) events
• Hypothyroidism (low thyroid hormone)
• Nausea

Bottom Line

• Lenvatinib was approved by the FDA in August 2018 to be used alone as the first treatment for a type of liver cancer called hepatocellular carcinoma (HCC) when it cannot be removed by surgery.
• In studies that compared lenvatinib with sorafenib as first-line treatment in patients with inoperable liver cancer, the primary endpoint, overall survival (OS), was found to be non-inferior (13.6 months compared to 12.3 months with sorafenib). In other words, lenvatinib did not show an improvement in survival (how long patients lived) when statistically compared to sorafenib.
• Side effects of treatment are common and may led to treatment interruption or discontinuation.

This is not all the information you need to know about lenvatinib and sorafenib for safe and effective use. Review the full drug product information at the above links and discuss this information, and any questions you have, with your doctor or other health care provider.