Tyverb

Summary

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/58682/2015

EMEA/H/C/000795

EPAR summary for the public

Tyverb

lapatinib

This document is a summary of the European Public Assessment Report (EPAR) for Tyverb. 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 Tyverb.

What is Tyverb?

Tyverb is a cancer medicine that contains the active substance lapatinib. It is available as tablets

(250 mg).

What is Tyverb used for?

Tyverb is used to treat patients with breast cancer that has been shown to be 'expressing' large

amounts of HER2. This means that the cancer produces a specific protein called HER2 (also known as

ErbB2) in large quantities on the surface of the tumour cells. Tyverb is used in the following ways:

• in combination with capecitabine (another cancer medicine) when the cancer is advanced or metastatic and got worse following previous treatment including an anthracycline and a taxane (other types of cancer medicine), and following treatment of the patient's metastatic disease with trastuzumab (another cancer medicine). 'Advanced' means that the cancer has started to spread and 'metastatic' means that the cancer has already spread to other parts of the body;

• in combination with trastuzumab for advanced or metastatic cancer that does not respond to hormones (hormone receptor-negative disease), and which got worse when previously treated with a combination of trastuzumab and other cancer medicines (chemotherapy);

• in combination with an aromatase inhibitor (another type of cancer medicine) in women who have been through the menopause, when the cancer is metastatic and responds to hormones. This combination is used in women who do not currently need to receive standard chemotherapy to treat their cancer.

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The medicine can only be obtained with a prescription.

How is Tyverb used?

Tyverb should only be started by a doctor who has experience in giving cancer medicines.

The recommended dose of Tyverb is four tablets a day when used with trastuzumab, five tablets a day when it is used with capecitabine, and six tablets a day when taken with an aromatase inhibitor. All of the tablets must be taken together at the same time every day, at least one hour before or one hour after food. Each patient should take the medicine at the same time each day with respect to food, such as always before or always after a meal. The doctor may decide to interrupt or stop treatment in patients experiencing certain side effects, especially those affecting the heart, lungs or liver. If patients start to take Tyverb again, they may need to use a lower dose. Patients who stop taking Tyverb after developing severe liver problems should not start to take the medicine again.

How does Tyverb work?

The active substance in Tyverb, lapatinib, belongs to a group of medicines called protein kinase inhibitors. These compounds work by blocking enzymes known as protein kinases, which can be found in some receptors on the surface of cancer cells including HER2. HER2 is a receptor for a chemical messenger called epidermal growth factor which produces signals that stimulate the cancer cells to divide uncontrollably. By blocking these receptors, Tyverb helps to control cell division and growth of the cancer. About a quarter of breast cancers express HER2.

How has Tyverb been studied?

Tyverb was studied in three main studies involving women with breast cancer.

The first study involved 408 women with advanced or metastatic disease that was expressing large quantities of HER2 who had already been treated with anthracyclines, taxanes and trastuzumab but whose disease had got worse or come back. The study compared Tyverb in combination with capecitabine, with capecitabine taken alone.

The second study involved 1,286 women who had been through the menopause with metastatic breast cancer that was sensitive to hormones. 219 of the women had cancer that was expressing large quantities of HER2. The study compared Tyverb with placebo (a dummy treatment), both of which were taken together with letrozole (an aromatase inhibitor). The women had not received trastuzumab or an aromatase inhibitor before entering this study.

The third study involved 296 women with metastatic disease that got worse despite treatment with other cancer medicines (including anthracyclines and taxanes) and with combinations of cancer medicines plus trastuzumab. The study compared Tyverb alone with a combination of Tyverb plus trastuzumab.

In all the studies, the main measure of effectiveness was how long the patients lived without their disease getting worse, which was assessed in scans. The studies also looked at how long the patients survived.

What benefit has Tyverb shown during the studies?

Tyverb in combination with another cancer medicine was more effective than the comparator treatment in all studies.

In the first study, the women taking Tyverb in combination with capecitabine lived for an average of 23.9 weeks without their disease getting worse, as assessed by their doctors, compared with 18.3 weeks in the women taking capecitabine alone. Women taking Tyverb with capecitabine survived for an average of 75 weeks, and those taking capecitabine alone survived for an average of 64.7 weeks.

In the second study, the women whose cancer was expressing large quantities of HER2 taking Tyverb in combination with letrozole survived for an average of 35.4 weeks without their disease getting worse. This compared with 13 weeks in those taking placebo in combination with letrozole.

In the third study, women taking Tyverb with trastuzumab lived without their disease getting worse for 12 weeks on average, compared with 8.1 weeks in those taking Tyverb alone. In addition, women taking the combination survived for 14 months on average, compared with 9.5 months in those taking Tyverb alone.

What is the risk associated with Tyverb?

The most common side effects with Tyverb (seen in more than 25% of patients) are rash and side effects affecting the stomach and gut (such as diarrhoea, nausea (feeling sick) and vomiting). Palmarplantar erythrodysaesthesia (rash and numbness on the palms and soles) is also very common when Tyverb is taken with capecitabine. For the full list of all side effects and restrictions with Tyverb, see the package leaflet.

Why has Tyverb been approved?

The CHMP decided that Tyverb's benefits are greater than its risks and recommended that it be given marketing authorisation.

Tyverb was originally given 'conditional approval'. This means that there was more evidence to come about the effectiveness of the medicine. As the company has supplied the additional information necessary, the authorisation has been switched from conditional to full approval.

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

A risk management plan has been developed to ensure that Tyverb 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 Tyverb, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Tyverb

The European Commission granted a conditional marketing authorisation valid throughout the European Union for Tyverb on 10 June 2008. This was switched to a full marketing authorisation on 17 February 2015.

The full EPAR for Tyverb 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 Tyverb, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 01-2015.

Tyverb

EMA/58682/2015

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