What is afatinib?

• What afatinib is
• Afatinib in the UK
• Research into Afatinib
• Side effects of afatinib
• More information

Afatinib is a new drug that researchers are testing for a number of different types of cancer. It is also known as BIBW 2992. Most of the research so far has been looking at it as a treatment for advanced non small cell lung cancer. Researchers are also testing it as a treatment for other types of advanced cancer including head and neck cancer, breast cancer and prostate cancer. You take afatinib as a tablet.

Afatinib is a type of biological therapy called a protein tyrosine kinase inhibitor (TKI). Tyrosine kinases are proteins which stimulate cells to grow. Afatinib stops (inhibits) some of these proteins from working. They include

• ErbB1 (epidermal growth factor receptor – EGFR)
• ErbB2 (Her2)
• ErbB4 (Her4)

Research has shown that other types of TKIs such as gefitinib (Iressa) and erlotinib (Tarceva) can help to control non small cell lung cancer in some people. These drugs work in people who have changes in the cell that makes them produce too much of the protein EGFR. However, we know that these TKIs stop working after a while and the cancer starts to grow again. Afatinib works slightly differently and may be a helpful treatment after these treatments have stopped working.

Afatinib is not licensed yet in the UK. It is only available within clinical trials.

The National Institute for Health and Clinical Excellence (NICE) have said they will look at afatinib as a treatment for advanced non small cell lung cancer once it has been licensed.

All new drugs go through a detailed research process. Research in the laboratory finds out if a potential new drug harms cancer cells in any way. Then researchers look at whether it is safe to give to people, what the dose should be, and which side effects it causes.

A phase 3 trial called LUX-Lung 1 looked at afatinib for people with advanced non small cell lung cancer who had already had chemotherapy and either erlotinib or gefitinib. The trial compared afatinib and best supportive care with a dummy drug (placebo) and best supportive care. Best supportive care means that you have treatment to control cancer symptoms and improve your quality of life. It may include chemotherapy, steroids, and help with diet problems. The results of this trial were reported in October 2010 at a European conference. This research found that the cancer stopped growing for longer in the people who had afatinib. The cancers stopped growing for 3.3 months compared to just over 1 month in people having the dummy drug. Afatinib helped to control symptoms but did not help people to live longer.

A phase 2 trial called LUX-Lung 2 looked at giving afatinib to people whose cancers had changes in the EGFR gene. They had either had one course of chemotherapy which had stopped working or had not had chemotherapy. In over half of the people having afatinib treatment their cancer became smaller. This is similar to trials testing gefitinib and erlotinib. The average time before the cancer started to grow again in people who had afatinib was 14 months. This suggests that afatinib may be better at controlling the growth of the cancer for a longer time.

We need more research to confirm these findings. The LUX-Lung trials are a series of 8 trials testing afatinib in people with non small cell lung cancer. Some of these trials are comparing it with chemotherapy. Most of the trials have finished recruiting patients but are still ongoing, following the progress of those who took part. It will be sometime before the results will be available and we know how well afatinib works and for who.

LUX-Head and Neck 1 and 2 are phase 3 clinical trials. Lux-Head and Neck 1 is looking at whether afatinib helps people to live longer in people with recurrent or metastatic cancer who have had platinum chemotherapy. It is comparing afatinib to the chemotherapy drug methotrexate. In Lux-Head and Neck 2 the researchers are looking at whether afatinib improves survival in people with locally advanced disease after chemoradiotherapy.

Research into other types of cancer is at an earlier stage and it will be some time before we know how well it works for these cancers.

The side effects in trials so far have included

• Diarrhoea – most people in afatinib trials had diarrhoea and for just under 1 in 5 people (20%) it was severe
• Feeling sick or vomiting
• Skin changes – 8 out of 10 people (80%) had a rash, red, dry, itchy skin or acne. This was severe in 1 out of 10 people (10%) and they had to reduce the dose or stop treatment for a while
• A sore mouth in 6 out of 10 people (60%)
• Nail changes in about 4 out of 10 people (40%)
• Poor appetite in 3 out of 10 people (30%)
• Nose bleeds in about 2 out of 10 people (20%)

You can find detailed information about tyrosine kinase inhibitors in the section about biological therapies. There is also more information about lung cancer in the cancer types section.