Ramucirumab (Cyramza) for the treatment of advanced liver cancer


Ramucirumab (trade name: Cyramza) has been approved in Germany since September 2019 for the treatment of liver cancer in adults who have already had treatment with the drug sorafenib. Ramucirumab is a treatment option if the liver cancer is advanced or if surgery isn’t possible and the level of the tumor marker alpha-fetoprotein in the blood is very high (over 400 ng per ml).

Liver cancer (hepatocellular carcinoma) is caused by malignant changes in the cells of the liver. This type of cancer is typically caused by liver cirrhosis (liver damage due to scarring), which leads to a decline in the function of the liver. The cancer is usually not very noticeable at first. Symptoms such as nausea or loss of appetite often 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). Liver cancer is difficult to treat. By the time it is detected, it may have already grown so much that surgery is no longer effective enough.

The drug ramucirumab is an antibody that disrupts the formation of new blood vessels. This is believed to prevent the tumor from growing any more, stopping the disease from progressing.


Ramucirumab is given as a drip (infusion) every 2 weeks. Each infusion takes about 60 minutes. The dose is determined by your body weight and the side effects. Treatment is stopped if the cancer progresses or ramucirumab is no longer tolerated.

Other treatments

The other treatment options for adults with advanced liver cancer include the drug cabozantinib or best supportive care (BSC). BSC should be tailored to the patient’s individual needs, relieve symptoms such as pain, and improve their quality of life.


In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether ramucirumab has any advantages or disadvantages in the treatment of advanced liver cancer compared to cabozantinib or BSC.

The manufacturer provided two studies for the purpose of this comparison. In the studies, 316 patients received treatment with ramucirumab and 226 were given a placebo. Both groups also had BSC. The studies only included people who could no longer have surgery to cure the cancer (e.g. to remove the tumor) and whose liver function had only slightly worsened. Despite the advanced stage of the disease, the patients were otherwise in good general health at the beginning of the study. The study found the following for this group of patients:

What are the advantages of ramucirumab?

Life expectancy: The studies show that ramucirumab has an advantage here: In these groups, participants passed away within an average of about 8 months (median value), compared to 5 months in the placebo group.

Severe gastrointestinal problems: The studies suggest that ramucirumab has an advantage in terms of these severe side effects. About 9 out of 100 people who received ramucirumab had these side effects, compared to only 15 out of 100 people who received a placebo.

Hyperbilirubinemia (increased concentration of bilirubin in the blood): Bilirubin is formed by the breakdown of hemoglobin, the pigment that gives red blood cells their red color. The studies also suggest that ramucirumab has an advantage over the placebo in terms of this severe side effect.

What are the disadvantages of ramucirumab?

Severe high blood pressure: The studies suggest that ramucirumab has a disadvantage here: 11 out of 100 people who received ramucirumab had very high blood pressure as a side effect, compared to only 3 out of 100 people who received the placebo.

Headache: Here too, the studies suggest that it has a disadvantage: 18 out of 100 people who received ramucirumab had headaches, compared to only 6 out of 100 people who received the placebo.

The studies suggest that ramucirumab also has a disadvantage in terms of edemasin the lower legs or feet and diseases affecting the genitals and mammary glands.

No difference

Severe side effects: Although ramucirumab had some advantages and disadvantages in terms of certain severe side effects, this was not so for the severe side effects as a whole: About half of the people in each group had severe side effects. So there was no difference between ramucirumab and the placebo.

Treatment stopped due to side effects: There was no difference between the treatment groups here either.

What remains unanswered?

Symptoms of the disease, overall health and health-related quality of life: The manufacturer didn’t provide any suitable data on these aspects.

Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Ramucirumab (hepatocellular carcinoma) – Benefit assessment according to §35a Social Code Book V. Dossier assessment; Commission A19-73. November 28, 2019. (IQWiG reports; Volume 839).

IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. informedhealth.org can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.

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Created on December 19, 2019
Next planned update: 2022


Institute for Quality and Efficiency in Health Care (IQWiG, Germany)

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