Introduction

Lenvatinib (trade name: Lenvima) has been approved in Germany since August 2018 for the treatment of hepatocellular carcinoma (a type of liver cancer) in adults who have not previously had any systemic treatment. Lenvatinib is considered if the hepatocellular carcinoma is advanced or surgery is not an option.

Hepatocellular carcinoma is caused by malignant changes in the cells of the liver. Hepatocellular carcinoma is usually not very noticeable at first. General symptoms such as nausea or loss of appetite don’t occur until it reaches an advanced stage. Large tumors often cause tenderness on the right side of the upper abdomen. The tummy may also swell as a result of fluids there (ascites).

Hepatocellular carcinoma is difficult to treat. It may have grown so much that the cancer can no longer be treated through surgery.

Patients with hepatocellular carcinoma often also have cirrhosis, which makes the function of the liver increasingly worse. If the cirrhosis is advanced, it’s no longer possible to provide the best treatment for the cancer. The Child-Pugh score is used to show how advanced the liver cirrhosis is.

The goal of treatment with lenvatinib is to block various proteins, which stops tumor growth. The medication also aims to stop tumor growth directly in the cells of the liver.

Application

Lenvatinib is taken once a day in the form of a capsule. The exact dose will depend on the patient's body weight:

  • Weight under 60 kg: The recommended dose is 8 mg of lenvatinib per day (two 4 mg capsules).
  • Weight over 60 kg: The recommended dose is 12 mg per day (three 4 mg capsules).

The dose can be adjusted if side effects occur.

Other treatments

The standard treatment for adults with advanced or inoperable hepatocellular carcinoma who haven't yet had any systemic treatment depends on whether they have cirrhosis and, if so, how advanced it is.

  • Sorafenib is a possible standard treatment for patients who don't have cirrhosis or who only have mild cirrhosis (Child-Pugh class A).
  • Best supportive care (BSC) is an option for patients with moderate cirrhosis (Child-Pugh class B). This supportive care should be tailored to the patient's individual needs, relieve symptoms such as nausea, loss of appetite or pain, and improve quality of life.

Assessment

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether lenvatinib has any advantages or disadvantages compared with the standard treatments for people with advanced or inoperable hepatocellular carcinoma who have not yet had any systemic treatment.

The manufacturer didn't provide any data for patients with moderate cirrhosis (Child-Pugh class B). So it remains unclear whether lenvatinib has any advantages or disadvantages for this group of patients.

For patients who don't have cirrhosis or who only have mild cirrhosis (Child-Pugh class A), the manufacturer only provided one ongoing study involving nearly 1,000 participants. Half of the patients received lenvatinib, and the other half had treatment with sorafenib. A preliminary assessment shows the following:

What are the advantages of lenvatinib?

  • Role functioning: In this aspect of quality of life, the initial results suggest that patients who received lenvatinib feel less restricted in their everyday life, during their free time or at work than patients who were given sorafenib do.
  • Body image and nutritional status: In this aspect of quality of life, the initial results also suggest that patients who received lenvatinib feel better about their outward appearance and have fewer problems with eating than patients who were given sorafenib.
  • Diarrhea: The initial results here suggest that lenvatinib has an advantage over sorafenib in people under the age of 75: Diarrhea got worse on average (median value) after about five months in people under the age of 75 years who were given lenvatinib. In people under the age of 75 years who were given sorafenib, it already got worse after only about three months. No difference was found in patients over the age of 75, though.

What are the disadvantages of lenvatinib?

Cognitive functioning: In this aspect of quality of life, the initial results suggest that patients who received lenvatinib were less able to concentrate and remember things than patients who were given sorafenib.

No differences

  • Life expectancy: There was no difference between lenvatinib and sorafenib here. More than 70 out of 100 people died within an average (median) of 27 months.
  • Symptoms: There was also no difference between the treatment groups in terms of the following:
    • Exhaustion
    • Nausea and vomiting
    • Shortness of breath
    • Sleep problems
    • Loss of appetite
    • Constipation
    • Jaundice
    • Fever
    • Bloated belly
  • Health-related quality of life: No difference between the treatments was found in various aspects of quality of life:
    • Managing activities of daily living such as shopping or washing (physical functioning)
    • Emotions such as irritability, feeling “down,” worrying and feeling tense (emotional functioning)
    • Limitations in family life, when doing things with friends, and in other social activities (social functioning)
    • Limitations affecting sex life
  • Severe side effects and stopping treatment due to side effects: There were no differences between the treatments here, either.
  • Disease-related pain: No relevant difference was found between the treatments regarding disease-related pain. The data was inconsistent.

What remains unanswered?

  • General health: The manufacturer didn't provide any suitable data on how lenvatinib affects general health in comparison to sorafenib.
  • Side effects: No suitable data was available for various side effects, either. So it remains unclear how lenvatinib compares to sorafenib in terms of individual side effects.

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the review and the hearings received, the G-BA passed a resolution on the added benefit of lenvatinib (Lenvima).