Introduction

Cabozantinib (trade name: Cabometyx) has been approved in Germany since November 2018 for the treatment of advanced hepatocellular carcinoma in adults who have already had treatment with the drug sorafenib.

Hepatocellular carcinoma is caused by malignant changes in the cells of the liver. It is usually not very noticeable at first. Symptoms such as nausea or loss of appetite don’t occur until it reaches an advanced stage. Large tumors cause tenderness on the right side of the upper abdomen. The tummy may swell as a result of fluids building up there (ascites). This type of cancer is usually caused by liver cirrhosis (liver damage due to scarring), which leads to a decline in the function of the liver. Hepatocellular carcinoma is difficult to treat. By the time it is detected, it may have already grown so much that surgery is no longer a treatment option.

The goal of treatment with cabozantinib is to block various proteins (enzymes) in order to reduce tumor growth.

Application

Cabozantinib is available in tablet form, in doses of 20, 40, and 60 mg. The recommended dose is 60 mg a day. The dosage depends on how well the patient tolerates the drug and the side effects, and can be adjusted individually by a doctor. Treatment is stopped if the disease gets worse or if very severe side effects arise.

Other treatments

Best supportive care (BSC) is an option for adults with advanced hepatocellular carcinoma. This treatment should be tailored to the patient’s individual needs, relieve symptoms such as pain, and improve their quality of life.

Assessment

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of cabozantinib compared with BSC for the treatment of hepatocellular carcinoma in people who have already had treatment with sorafenib.

The manufacturer provided one study for the purpose of this comparison. The study involved one group of 512 patients who had treatment with cabozantinib and another group of 261 participants who received a dummy drug (a placebo). Both groups also had BSC. The study only included people who could no longer have surgery to cure the cancer, such as a liver transplant or removal of the tumor, and whose liver function had only slightly worsened. Despite the advanced stage of the disease, patients were otherwise in good general health. The study produced the following results for these patients:

What are the advantages of cabozantinib?

Life expectancy: The study suggests that cabozantinib has an advantage here: In this group, participants had passed away within an average of about 10 months (median value), compared to 8 months in the placebo group.

What are the disadvantages of cabozantinib?

  • Serious side effects: The study suggests that there is a disadvantage here. Serious side effects occurred in 84 out of 100 people who took cabozantinib, but only in about 51 out of 100 people who took a placebo.
  • These serious side effects included:
    • Disorders of the nervous system
    • Loss of appetite
    • Diarrhea
    • Exhaustion
    • High blood pressure
    • Hand-foot syndrome
  • Treatment stopped due to side effects: The study suggests that cabozantinib has a disadvantage here. 35 out of 100 participants in this group stopped their treatment mainly due to severe side effects, compared to only about 18 out of 100 people in the placebo group.
  • Inflammation of the mucous membranes: The study suggests that cabozantinib has a disadvantage in terms of this side effect, too.

No differences

There was no noticeable difference between cabozantinib and the placebo in terms of general health.

What remains unanswered?

Health-related quality of life: The manufacturer didn't provide any data about quality of life.

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 cabozantinib (Cabometyx).