o

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/526432/2016

EMEA/H/C/002489

EPAR summary for the public

Xaikori

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. It is used if the NSCLC is 'ALK-positive', which means that the cancer cells contain certain changes affecting the gene responsible for a protein called ALK (anaplastic lymphoma kinase). It is also used when the NSCLC is 'ROS1-positive'. This means that the cancer cells contain changes affecting the gene responsible for the protein ROS1.

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 cancer medicines. The presence of the genetic changes affecting ALK ('ALK-positive' status) or ROS1 ('ROS1-positive' status) has to be confirmed in advance by appropriate methods.

The recommended dose is 250 mg twice per day. 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. Doses may

30 Churchill Place • Canary Wharf • London E14 5EU • United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact

© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.

need to be delayed or treatment stopped altogether if the patient develops certain severe side effects. Doses may need to be adjusted in patients with severely reduced kidney function and the medicine must not be used in patients with severely reduced liver function.

For further information, see the package leaflet.

How does Xalkori work?

ALK and ROS1 belong to a family of proteins called receptor tyrosine kinases (RTKs), which are involved in the growth of cells. In patients either 'ALK-positive' or 'ROS1-positive', the ALK or ROS1 protein is abnormally active and can promote the growth of cancer cells 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 or ROS1, including when the genetic change is present, thereby reducing the growth and spread of the cancer in ALK-positive or in ROSl-positive NSCLC.

How has Xalkori been studied?

Xalkori was investigated in patients with ALK-positive NSCLC who had been treated before with other cancer medicines. The study involved 347 patients with ALK-positive NSCLC and compared Xalkori with 1 of 2 cancer medicines (either pemetrexed or docetaxel). The main measure of effectiveness was the length of time that patients lived without the disease getting worse.

In addition, Xalkori was investigated in patients who had not received treatment for their NSCLC before. The study involved 343 patients with ALK-positive NSCLC and compared Xalkori with other cancer medicines (pemetrexed with either cisplatin or carboplatin). The main measure of effectiveness was the length of time that patients lived without the disease getting worse.

Xalkori was also investigated in one study in 53 ROSl-positive patients with advanced disease. The main measure of effectiveness was based on the percentage of patients who responded completely or partially to treatment. All the patients in this study were treated with Xalkori; the majority of them had been previously treated with other cancer medicines.

What benefit has Xalkori shown during the studies?

In the study in previously treated patients, those treated with Xalkori lived on average for nearly 8 months without their disease getting worse compared with 3 months in patients who were treated with either pemetrexed or docetaxel.

In the study in previously untreated patients, those treated with Xalkori lived on average for nearly 11 months without their disease getting worse compared with 7 months in patients who were treated with pemetrexed-containing therapy.

In the study in ROSl-positive patients, around 70% of patients (37 out of 53) responded completely or partially to treatment. This is considered a favourable response when compared with response rates of around 20 to 30% to previous treatments, in those patients who had been given them. For the previously untreated patients, 6 out of 7 responded to treatment.

What is the risk associated with Xalkori?

The most common side effects with Xalkori (seen in more than 1 in 4 patients) are visión problems, nausea (feeling sick), diarrhoea, vomiting, oedema (swelling), increases in liver enzymes in the blood, decreased appetite, constipation, dizziness, neuropathy (pain due to nerve damage) and fatigue. The most serious side effects are liver toxicity, pneumonitis (lung inflammation), neutropenia (low blood levels of neutrophils, a type of white blood cell) and prolonged QT interval (a problem with the electrical activity of the heart). For the full list of all side effects reported with Xalkori, see the package leaflet.

Xalkori must not be used in patients with severely reduced liver function. For the full list of restrictions, see the package leaflet.

Why has Xalkori been approved?

The CHMP concluded that treatment with Xalkori has a beneficial effect on the length of time the patients with ALK-positive NSCLC lived without the disease getting worse, irrespective of whether they were previously treated. For patients with ROSl-positive NSCLC, for whom no specific treatments are currently available, the CHMP noted the evidence of a high response rate, in particular for patients who had previously received other cancer treatments.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 on 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 final results of a study in patients with ALK-positive NSCLC comparing the safety and effectiveness of Xalkori and chemotherapy treatments, to confirm how long patients lived overall. Additional safety data from this study will also be provided.

What measures are being taken to ensure the safe and effective 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.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Xalkori have also been included in the summary of product characteristics and the package leaflet.

Other information about Xalkori

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

The full EPAR for Xalkori can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Xalkori, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 08-2016.

Xalkori

EMA/526432/2016

Page 4/4