Introduction

Ceritinib (trade name: Zykadia) has been approved in Germany since May 2015 for the treatment of a specific type of advanced lung cancer. It can be used in adults who have cancer cells with a particular mutation that can lead to faster tumor growth, and who were previously treated with the drug crizotinib after chemotherapy. Since March 2017, the drug has also been available for people who haven't had treatment before and who can't have surgery, radiotherapy or chemoradiotherapy.

Lung cancer is caused by the growth of malignant cells in the airways (bronchi) and their branches (bronchioles). It is also referred to as a bronchogenic carcinoma. There are two main types of tumors:

  • Small-cell lung cancer, SCLC
  • Non-small-cell lung cancer, NSCLC

NSCLC is surgically removed, if possible. But sometimes it is already too large or has spread to other parts of the body (metastasis) through the blood or lymphatic system. It is then called advanced lung cancer.

Some people with non-small-cell lung cancer have an abnormal enzyme in the tumor tissue called anaplastic lymphoma kinase (ALK). The full name of the cancer is then ALK-positive non-small-cell lung cancer. The enzyme ALK can lead to uncontrolled growth of the tumor tissue.

Treatment with ceritinib aims to inhibit the enzyme ALK, thereby inhibiting further tumor growth.

Application

Ceritinib is taken once a day, at the same time every day, in the form of a capsule. One capsule contains 150 mg. The daily dose depends on how well the drug is tolerated: The lowest possible daily dose of the drug is 300 mg, the highest 750 mg. The treatment is ended if the side effects become too severe.

Other treatments

The standard first-line treatment for people with advanced ALK-positive non-small-cell lung cancer who can't have either surgery or chemoradiotherapy is the drug crizotinib.

Depending on their general state of health, people who have already been treated with chemotherapy and crizotinib have various treatment options: either more chemotherapy with docetaxel or pemetrexed, or best supportive care (BSC). Supportive care should be tailored to the patient's individual needs, relieve symptoms such as pain, and improve quality of life.

Assessment

In 2017, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of ceritinib for the groups of people mentioned above when compared with standard treatments.

No relevant data was available for the following groups:

  • People with ALK-positive non-small-cell lung cancer who have not had treatment before
  • People with ALK-positive non-small-cell lung cancer who have had chemotherapy and treatment with crizotinib before and who cannot have chemotherapy again

It is therefore not possible to tell whether ceritinib has any advantages or disadvantages for these groups when compared with standard treatments.

The manufacturer provided one study for people with ALK-positive non-small-cell lung cancer who have had treatment with crizotinib before and who can have chemotherapy again. In the study, 116 people had chemotherapy with docetaxel or pemetrexed, and the other group of 115 people had treatment with ceritinib. The people involved had had treatment at least twice before. The study found the following:

What are the advantages of ceritinib?

  • Health-related quality of life: The study shows weak evidence that patients who had treatment with ceritinib reported better physical and social functioning as well as role functioning than those who had chemotherapy. No difference was found regarding other aspects of quality of life, such as emotional or cognitive functioning, as well as general status of health.
  • Symptoms: Cancer and treatments for cancer can cause a number of different problems. Hair loss, coughing or neural disorders developed later in patients who had treatment with ceritinib than in patients who had chemotherapy. The same is true for pain such as shoulder or arm pain, or pain affecting the mucous membranes of the mouth. There was no difference regarding chest pain.
  • Serious side effects: In terms of serious disorders of the blood and lymphatic system, muscles, bones and connective tissue, there was weak evidence that ceritinib causes these side effects later than chemotherapy does. The study also provided weak evidence that ceritinib has an advantage concerning the following side effects:
    • Trouble taking the drugs
    • Psychiatric disorders
    • Problems affecting the nervous system, airways and chest

What are the disadvantages of ceritinib?

  • Gastrointestinal diseases: The study showed weak evidence that ceritinib has a disadvantage here. Symptoms such as nausea, vomiting and diarrhea developed earlier during treatment with ceritinib than during treatment with docetaxel or pemetrexed. Nausea and vomiting, for example, got worse after about a month in people receiving ceritinib and after about 6 months in people receiving the standard treatment.

No difference

  • Life expectancy: No difference was found here. In both groups, half the participants had passed away within about 18 to 20 months.
  • No difference between the treatments was found regarding these symptoms of lung cancer:
    • Breathing problems
    • Exhaustion
    • Insomnia
    • Coughing up blood
    • Constipation
    • Trouble swallowing
    • Loss of appetite
  • Treatment stopped due to side effects: There was also no difference here.

More information

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