Xalkori

crizotinib

This is a summary of the European public assessment report (EPAR) for Xalkori. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Xalkori.

What is Xalkori?

Xalkori is a medicine that contains the active substance crizotinib. It is available as capsules (200 mg and 250 mg).

What is Xalkori used for?

Xalkori is used to treat adults with a type of lung cancer called non-small-cell lung cancer (NSCLC), when the disease is advanced and has already been treated before. It is only used if the NSCLC is ‘ALK-positive’, which means that the cancer cells contain certain defects affecting the gene responsible for a protein called ALK (anaplastic lymphoma kinase).

The medicine can only be obtained with a prescription.

How is Xalkori used?

Treatment with Xalkori should be started and supervised by a doctor who is experienced in using anticancer medicines. The presence of the genetic defect affecting ALK (‘ALK-positive’ status) has to be confirmed in advance by appropriate methods.

The recommended dose is 250 mg twice per day, until the disease progresses or treatment cannot be tolerated due to side effects. If certain side effects develop, the doctor may decide to interrupt or reduce the dose to 200 mg twice per day then to 250 mg once per day. In certain cases, treatment should be permanently stopped, including if the patient has a severely prolonged QT interval (an alteration of the electrical activity of the heart).

The capsules should not be taken with grapefruit juice or St John’s wort, as these can alter the amount of active substance in the patient’s blood.

How does Xalkori work?

ALK belongs to a family of proteins called receptor tyrosine kinases (RTKs), which are involved in the growth and spread of certain cancers and the development of new blood vessels that supply them. The active substance in Xalkori, crizotinib, is an RTK inhibitor. It works mainly by blocking the activity of ALK, including when the genetic defect is present, thereby reducing the growth and spread of the cancer in ALK-positive NSCLC.

How has Xalkori been studied?

The effects of Xalkori were first tested in experimental models before being studied in humans.

Xalkori was investigated in two main studies involving 386 patients with ALK-positive NSCLC who had been treated before. Xalkori was not compared with any other treatment. In both studies, the main measure of effectiveness was the percentage of patients who responded completely or partially to treatment. Response to treatment was assessed using body scans and standardised criteria used for solid tumours. A complete response is when a patient has no signs of the cancer. Other factors were also taken into consideration, including the length of time the patients lived without the disease getting worse.

What benefit has Xalkori shown during the studies?

Xalkori was shown to be effective in treating ALK-positive NSCLC, with 60% of the patients in the first study and 53% in the second study responding completely or partially to treatment. The length of time the patients lived without the disease getting worse in the two studies was 9.2 and 8.5 months respectively.

What is the risk associated with Xalkori?

The most common side effects with Xalkori (seen in more than 1 in 5 patients) are vision problems, nausea (feeling sick), diarrhoea, vomiting, oedema (swelling), constipation and fatigue. For the full list of all side effects reported with Xalkori, see the package leaflet.

Xalkori must not be used in people who are hypersensitive (allergic) to crizotinib or any of the other ingredients. It must not be used in patients with severely reduced liver function.

Why has Xalkori been approved?

The CHMP concluded that the available study results showed that treatment with Xalkori has a beneficial effect, and noted that this was supported by updated data on the survival of patients and the preliminary results of a larger study. Therefore the CHMP decided that Xalkori’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Xalkori has been given ‘conditional approval’. This means that there is more evidence to come about the medicine, in particular data from a larger study and the longer term outcomes of patients included in the studies already considered. Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

What information is still awaited for Xalkori?

The company that markets Xalkori will provide the results of an ongoing study in patients with ALK-positive NSCLC comparing the safety and effectiveness of Xalkori with chemotherapy treatments. The company will also provide updated results from the two main studies already assessed by the CHMP, including how long the patients lived overall and how long they lived without their disease getting worse. Additional safety data from these ongoing studies will also be provided.

What measures are being taken to ensure the safe use of Xalkori?

The company that markets Xalkori will ensure that doctors who are expected to prescribe Xalkori receive educational material containing important safety information about the medicine, including the risk of QT prolongation, and a patient alert card.

Other information about Xalkori

The European Commission granted a marketing authorisation valid throughout the European Union for Xalkori on 23 October 2012.

For more information about treatment with Xalkori, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 31/05/2013 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

25/04/2013  Xalkori -EMEA/H/C/002489 -II/0002

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Antineoplastic agents

Therapeutic indication

Xalkori is indicated for the treatment of adults with previously treated anaplastic-lymphoma-kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC).

Changes since initial authorisation of medicine

Initial marketing-authorisation documents