Cyramza

Summary

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/42349/2016

EMEA/H/C/002829

EPAR summary for the public

Cyramza

ramucirumab

This is a summary of the European public assessment report (EPAR) for Cyramza. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Cyramza.

For practical information about using Cyramza, patients should read the package leaflet or contact their doctor or pharmacist.

What is Cyramza and what is it used for?

Cyramza is a cancer medicine used to treat adult patients with:

• advanced gastric cancer (cancer of the stomach) or cancer of the area where the gullet (oesophagus) enters the stomach (known as gastro-oesophageal junction adenocarcinoma). Cyramza is used in combination with another medicine, paclitaxel, or on its own if the combination with paclitaxel is not appropriate, in patients whose disease has worsened despite treatment with medicines containing platinum or fluoropyrimidines;

• metastatic colorectal cancer (cancer of the large bowel that has spread to other parts of the body). Cyramza is used with 'FOLFIRI' chemotherapy (a combination of fluorouracil, folinic acid and irinotecan) in patients whose disease has worsened despite treatment with bevacizumab, oxaliplatin and a fluoropyrimidine;

• non-small cell lung cancer that is advanced or has spread to other parts of the body. Cyramza is used in combination with docetaxel in patients whose disease has worsened despite treatment with medicines containing platinum.

Cyramza contains the active substance ramucirumab.

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How is Cyramza used?

Cyramza is available as a concentrate to be made up into a solution for infusion (drip) into a vein. It can only be obtained with a prescription and treatment should be started and supervised by a specialist who has experience in the treatment of cancer.

When given in combination with paclitaxel, the recommended dose is 8 mg per kg body weight given on days 1 and 15 of a 28-day cycle, before being given the infusion of paclitaxel (which is given on days 1, 8 and 15).

When given as a single medicine or with FOLFIRI, the recommended dose of Cyramza is 8 mg per kg body weight given every two weeks.

When given in combination with docetaxel, the recommended dose is 10 mg per kg body weight given on day 1 of a 21-day cycle, before being given the infusion of docetaxel.

Treatment should continue for as long as possible, until the disease worsens or the side effects become too severe. For more information, see the package leaflet.

How does Cyramza work?

The active substance in Cyramza, ramucirumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) in the body.

Ramucirumab has been designed to attach to a receptor for a protein called vascular endothelial growth factor (VEGF). The VEGF receptor can be present at high levels in tumours and helps in the development of new blood vessels that supply the tumours. By attaching to it, ramucirumab blocks this action, reducing the blood supply to the tumour and so slowing the growth of the cancer.

What benefits of Cyramza have been shown in studies?

Cyramza has been shown to increase survival of patients with advanced gastric or gastro-oesophageal junction cancer, metastatic colorectal cancer and advanced or metastatic non-small cell lung cancer whose disease has worsened despite treatment with other medicines in 4 main studies.

In one main study involving 665 patients with advanced gastric or gastro-oesophageal junction cancer which worsened despite treatment with medicines containing platinum and fluoropyrimidine, those treated with Cyramza and paclitaxel lived significantly longer on average than patients treated with paclitaxel and placebo (a dummy treatment): 9.6 months versus 7.4 months respectively. Similarly, in another study in 355 patients, those treated with Cyramza plus best supportive care lived significantly longer than patients treated with placebo plus best supportive care (an average of 5.2 months versus 3.8 months, respectively).

In a main study involving 1,072 patients with metastatic colorectal cancer which worsened despite treatment with bevacizumab, oxaliplatin and a fluoropyrimidine, those treated with Cyramza and FOLFIRI lived longer on average than patients treated with FOLFIRI and placebo: 13.3 months versus 11.7 months respectively.

In a main study involving 1,253 patients with advanced or metastatic non-small cell lung cancer which worsened despite treatment with medicines containing platinum, those treated with Cyramza and docetaxel lived longer on average than patients treated with docetaxel and placebo: 10.5 months versus 9.1 months respectively.

What are the risks associated with Cyramza?

The most common side effects with Cyramza (which may affect more than 1 in 10 people) include fatigue (tiredness) or weakness, leucopenia (low white blood cell counts), neutropenia (low counts of a particular type of white blood cell), diarrhoea, epistaxis (nosebleeds) and stomatitis (inflammation of the lining of the mouth). The most serious adverse effects reported (either of Cyramza alone or in combination with other cancer medicines) included gastrointestinal perforation (a hole that develops in the wall of the gut), severe gastrointestinal haemorrhage (bleeding from the gut) and arterial thromboembolic events (problems caused by blood clots and blockage of the arteries). For the full list of all side effects with Cyramza, see the package leaflet.

When used for lung cancer, Cyramza must not be used when there is a cavity in the cancer or if the cancer is close to a major blood vessel. For the full list of restrictions, see the package leaflet.

Why is Cyramza approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Cyramza's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted that the benefit of Cyramza in prolonging the lives of gastric and gastro-oesophageal junction cancer patients was clearly demonstrated when Cyramza was given with paclitaxel. The benefit was smaller when Cyramza was given on its own, but this could still be a therapeutic option when treatment with paclitaxel is not considered appropriate. Cyramza was also shown to prolong survival of patients with colorectal and non-small cell lung cancer. Although the effects were modest, the size of the benefit was considered clinically relevant given the normally poor prognosis in these patients.

The safety profile of Cyramza is in line with what is expected for other medicines blocking VEGFR activity and considered manageable.

What measures are being taken to ensure the safe and effective use of Cyramza?

A risk management plan has been developed to ensure that Cyramza is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Cyramza, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Cyramza will carry out a study on the safety of Cyramza when used on its own for gastric cancer, including at doses higher than the approved dose, and a study to try to further characterise those patients with colorectal cancer who may respond better to Cyramza.

Further information can be found in the summary of the risk management plan.

Other information about Cyramza

The European Commission granted a marketing authorisation valid throughout the European Union for Cyramza on 19 December 2014.

The full EPAR and risk management plan summary for Cyramza 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 Cyramza, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 02-2016.

Cyramza

EMA/42349/2016

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