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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/170285/2015

EMEA/H/C/000741

EPAR summary for the public

Vectibix

panitumumab

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

What is Vectibix?

Vectibix is a cancer medicine that contains the active substance panitumumab. It is available as a concentrate that is made up into a solution for infusion (drip) into a vein.

What is Vectibix used for?

Vectibix is used to treat metastatic cancer of the colon or rectum. This is cancer of the large intestine (bowel) that has spread to other parts of the body. Vectibix is used in patients whose tumour cells contain the most common form (non-mutated or wild-type) of RAS. RAS is a family of genes that includes those known as KRAS and NRAS; when mutated (altered) forms of RAS are present in tumour cells they can stimulate tumour growth. About half of the patients with metastatic cancer of the colon or rectum have wild-type RAS tumours. Vectibix is used alone or with combinations of other cancer medicines that include a 'fluoropyrimidine' such as the medicine 5-fluorouracil, specifically:

•    in combination with 'FOLFOX' chemotherapy (a combination of 5-fluorouracil with folinic acid and the cancer medicine oxaliplatin) or 'FOLFIRI' chemotherapy (5-fluorouracil with folinic acid and a different cancer medicine, irinotecan) as first-line treatment (in patients who have not been treated before);

•    in combination with 'FOLFIRI' chemotherapy as second-line treatment (in patients who have already received fluoropyrimidine-based chemotherapy but not irinotecan);

•    on its own after treatment has stopped working with combinations of cancer medicines that include a fluoropyrimidine, oxaliplatin and irinotecan.

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The medicine can only be obtained with a prescription.

How is Vectibix used?

Treatment with Vectibix should be supervised by a doctor who has experience in the use of cancer therapy. It should only be started after the presence of wild-type RAS (KRAS and NRAS genes) has been confirmed by an experienced laboratory using a validated test method.

The recommended dose of Vectibix is 6 mg per kilogram body weight given once every two weeks as an infusion. The recommended infusion time is approximately 60 minutes, but larger doses may need 90 minutes. The dose may need to be modified if severe skin reactions occur.

How does Vectibix work?

The active substance in Vectibix, panitumumab, 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) that is found on certain cells in the body. Panitumumab has been designed to attach to EGFR, which can be found on the surface of certain cells, including cells in some tumours. As a result, these tumour cells can no longer receive the messages transmitted via EGFR that they need for growth, progression and spreading to other parts of the body (metastasis).

Panitumumab does not seem to work in tumour cells that contain mutated RAS genes. This is because growth of these types of cells does not depend on EGFR and they can continue to grow uncontrollably even when EGFR is blocked.

How has Vectibix been studied?

Vectibix has been studied in five main studies in patients with metastatic cancer of the colon or rectum:

•    Vectibix in combination with FOLFOX has been investigated in a main study involving 1,183 patients who had not been treated before for their metastatic cancer, where Vectibix was compared with chemotherapy alone. The main measure of effectiveness was progression-free survival (how long a patient lived without the disease getting worse).

•    Vectibix in combination with FOLFIRI has been investigated in a study involving 154 previously untreated patients which looked mainly at the percentage of patients who responded to treatment. Response to treatment was measured as complete or partial lack of signs of cancer.

•    Another study in 80 previously untreated patients compared Vectibix and FOLFIRI with Vectibix in combination with FOLFOX. This study also looked mainly at the percentage of patients who responded to treatment.

•    Vectibix in combination with FOLFIRI has been investigated in a main study involving 1,186 patients who had been treated before, where Vectibix was compared with chemotherapy alone.

The main measures of effectiveness were progression-free survival and overall survival (the length of time the patients lived).

•    Vectibix on its own has been investigated in a study involving a total of 463 patients whose disease had got worse during or after previous treatment that included a fluoropyrimidine, oxaliplatin and irinotecan. The effects of Vectibix in addition to 'best supportive care' were compared with those of best supportive care alone. Best supportive care is any medicines or techniques to help patients,

Vectibix

such as antibiotics, painkillers, transfusions and surgery, but not other cancer medicines. The main measure of effectiveness was progression-free survival.

What benefit has Vectibix shown during the studies?

Vectibix has been shown to be effective at treating patients with metastatic cancer of the colon or rectum when used together with other cancer medicines and on its own:

•    In the first study, previously untreated patients with wild-type RAS receiving Vectibix in combination with FOLFOX lived for an average of 10.1 months without the disease getting worse compared with 7.9 months for patients receiving FOLFOX alone.

•    In the second study, around 59% of previously untreated patients with wild-type RAS who were given Vectibix plus FOLFIRI responded to treatment. These patients lived for an average of 11.2 months without their disease getting worse.

•    In the third study, around 73% of previously untreated patients with wild-type RAS given Vectibix and FOLFIRI responded to treatment. This is similar to a response rate of 78% observed in patients with wild-type RAS given Vectibix with FOLFOX. Patients given Vectibix with FOLFIRI lived for an average of 14.8 months while patients given Vectibix with FOLFOX lived for an average of 12.8 months without their disease getting worse.

•    In the fourth study, previously treated patients with wild-type RAS receiving Vectibix in combination with FOLFIRI lived for 16.2 months compared with 13.9 months in patients receiving FOLFIRI alone. Patients receiving Vectibix also had a longer period of time without their disease getting worse: 6.4 months versus 4.6 months.

•    In the fifth study, patients with wild-type KRAS in their tumours who received Vectibix on its own but in addition to best supportive care lived for an average of 16.0 weeks without their disease getting worse. This compared with 8.0 weeks in those who received best supportive care alone. In contrast, there was no effect of Vectibix in the patients with mutated KRAS in their tumours, with both groups of patients living for an average of around 8.0 weeks without their disease getting worse. It was later confirmed that benefit is limited only to patients with wild-type RAS tumours, rather than patients with mutant RAS tumours.

What is the risk associated with Vectibix?

In studies, 93% of the patients receiving Vectibix had side effects affecting the skin, although most of these were mild or moderate. The most common side effects with Vectibix (seen in more than 2 patients in 10) are diarrhoea, nausea (feeling sick), vomiting, constipation, abdominal pain (stomach ache), fatigue (tiredness), pyrexia (fever), lack of appetite, paronychia (nail bed infection), rash, acneiform dermatitis (skin inflammation resembling acne), pruritus (itching), erythema (reddening of the skin) and dry skin. For the full list of all side effects reported with Vectibix, see the package leaflet.

Vectibix must not be used in patients who have had a severe or life-threatening hypersensitivity (allergic) reaction to panitumumab or any of the other ingredients in the past. It must not be used in patients with interstitial pneumonitis or pulmonary fibrosis (lung diseases). Vectibix must not be used with oxaliplatin-containing chemotherapy in patients whose tumour contains the mutated RAS gene or for whom the RAS status is not known.

Why has Vectibix been approved?

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

Vectibix was originally given 'conditional approval' because there was more evidence to come about 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 Vectibix?

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

The company that markets Vectibix will also ensure that all doctors who are expected to prescribe Vectibix are provided with educational material informing them of the importance of carrying out a RAS test before treatment with Vectibix and only using Vectibix in patients whose tumour is confirmed to contain the wild-type RAS gene. In addition, the company will provide the results of studies to try to further characterise those patients who respond better to Vectibix.

Other information about Vectibix:

The European Commission granted a conditional marketing authorisation valid throughout the European Union for Vectibix on 3 December 2007. This was switched to a full marketing authorisation on 15 January 2015.

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

This summary was last updated in 03-2015.

Vectibix

EMA/170285/2015

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