Entrectinib (Rozlytrek)

Entrectinib is a type of targeted drug. It is pronounced en-trek-ti-nib. You might also hear it called either a:

• histology independent therapy (HIT)

• tumour agnostic therapy

HITs are a newer type of treatment. They treat cancers with specific gene changes. Usually, cancers are treated depending on where they start in the body.

Entrectinib is a treatment for:

• solid cancers that have a neurotrophic tyrosine receptor kinase (NTRK) gene change

• non small cell lung cancer with a ROS1-positive gene change

You might have entrectinib for a solid cancer if:

• your cancer is locally advanced or advanced (metastatic)

• surgery to remove the cancer could cause severe health problems

• you haven’t had treatment with another NTRK targeted drug

• other treatments have not worked or are not suitable for you

For non-small cell lung cancer, you might have entrectinib if:

• your cancer is advanced (metastatic)

• you haven’t had treatment with another ROS1 targeted drug

How does entrectinib work?

Entrectinib is a type of ​targeted drug​ called a ​tyrosine kinase inhibitor (TKI)​ . ​Tyrosine kinases​ are proteins that cells use to signal to each other to grow. They act as chemical messengers. Blocking these signals helps to slow or stop the cancer from growing.

There are several different tyrosine kinases. You have tests on your cancer cells before you have this treatment. The tests look for changes in these proteins or ​genes​ . With entrectinib they look for the NTRK and ROS1 gene changes.

How do you take entrectinib?

You take entrectinib as capsules that you swallow. You swallow the capsules whole with a glass of water. You can take them with or without food.

You should take the right dose, not more or less.

Talk to your healthcare team before you stop taking a cancer drug, or if you have missed a dose.

How often do you take entrectinib?

You take entrectinib once a day.

You take entrectinib for as long as it’s working and the side effects aren’t too bad.

What are the side effects of entrectinib?

Side effects can vary from person to person. They also depend on what other treatments you're having. 

When to contact your team

Your doctor, nurse or pharmacist will go through the possible side effects. They will monitor you during treatment and check how you are at your appointments. Contact your advice line as soon as possible if:

• you have severe side effects 

• your side effects aren’t getting any better

• your side effects are getting worse

Early treatment can help manage side effects better. 

We haven't listed all the side effects here. Talk to your healthcare team if you have any new symptoms that you think might be a side effect of your treatment.

Remember it is very unlikely that you will have all of these side effects. But you might have some of them at the same time.

Common side effects

These side effects happen in more than 10 in 100 people (more than 10%). You might have one or more of them. They include:

Increased risk of infection

Increased risk of getting an infection is due to a drop in white blood cells. Symptoms include a change in temperature, aching muscles, cough, headaches, feeling cold and shivery, pain or a burning feeling when peeing, or generally feeling unwell. You might have other symptoms depending on where the infection is.

Infections can sometimes be life threatening. You should contact your advice line urgently if you think you have an infection. 

High temperature

You might get a high temperature (fever) for a few hours after having this treatment. Tell your doctor or nurse if you have a fever.

Breathlessness and looking pale

You might be breathless and look pale due to a drop in red blood cells. This is called anaemia.

Weight gain

You may gain weight while having this treatment. You may be able to control it with diet and exercise. Tell your healthcare team if you are finding it difficult to control your weight. 

Loss of appetite

You might not feel like eating. It is important to eat as much as you can. Eating several small meals and snacks throughout the day can be easier to manage. You can talk to a dietitian if you are concerned about your appetite.

Taste changes

Taste changes may make you go off certain foods and drinks. You may also find that some foods taste different from usual or that you prefer to eat spicier foods. Your taste gradually returns to normal a few weeks after your treatment finishes.

Dizziness

This drug might make you feel dizzy. You might also feel dizzy when standing or moving around. Or it might feel like the world is spinning.

Don’t drive or operate machinery if you have this.

Abnormal sensations when touching or being touched

You might experience pain, an unpleasant feeling or nothing when touching something. Or you might experience a pricking or burning sensation when being touched.

Take extra care when touching hot or sharp objects.

Thinking and memory problems (cognitive disorders)

You might have problems with thinking, learning, remembering, using your judgment and making decisions. Let your doctor or nurse know if you experience this.

Headaches

Tell your healthcare team if you keep getting headaches. They can give you painkillers to help.

Numbness of fingers and toes

Numbness or tingling in fingers or toes is often temporary and can improve after you finish treatment. Tell your healthcare team if you're finding it difficult to walk or complete fiddly tasks such as doing up buttons. 

Problems with balance, walking and speech

Different parts of your body might be affected. You might have problems with:

• balance and walking

• speaking

• swallowing

• writing and eating

• your vision

Tell your healthcare team if you have any of these symptoms.

Sleeping problems

You might fall asleep during the day (hypersomnia), have problems falling and staying asleep at night (insomnia) or feel drowsy.

It is important not to use machinery when feeling sleepy or drowsy. Speak to your doctor or nurse if you have sleeping problems. They can give advice on what to do. 

Eyesight changes

You might have blurred vision or loss of vision. Speak to your doctor or nurse if you are worried about this.

Low blood pressure

Tell your doctor or nurse if you feel lightheaded or dizzy. Your blood pressure might also drop when standing up (orthostatic hypotension). Take extra care when standing up quickly.

You have your blood pressure checked regularly.

Breathlessness and a cough

Tell your doctor or nurse if you’re breathless or have a cough. This could be due to an infection, such as pneumonia. Or it could be caused by changes to the lung tissue, making it less flexible.

Diarrhoea or constipation

Tell your healthcare team if you have diarrhoea or constipation. They can give you medicine to help. 

Feeling or being sick

Feeling sick is usually mild. Anti sickness tablets can control it if you need them. Tell your doctor or nurse if you feel sick. 

Tummy (abdominal) cramps

Tell your treatment team if you have this. They can check the cause and give you medicine to help. 

Difficulty swallowing

Liver changes

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes.

You have regular blood tests to check for any changes in the way your liver is working.

Skin changes

You might notice skin changes, such as dryness, redness, itching and rashes similar to acne on your face, neck and trunk. 

Tell your doctor if you have any rashes or itching. Don't go swimming if you have a rash because the chlorine in the water can make it worse.

If your skin gets dry or itchy, using unperfumed moisturising cream may help. Check with your doctor or nurse before using any creams or lotions. Wear a high factor sun block if you’re going out in the sun.

Less commonly, your skin might become very sensitive to sunlight. Symptoms can include a rash or sunburn and your skin might itch, blister or peel.

Pain

You might feel some pain in your muscles and joints. Or you might have pain in your back, neck, chest, bones, or arms and legs.

Speak to your healthcare team about what painkillers you can take to help with this.

Muscle weakness

This drug can cause muscle weakness (myasthenia) in different parts of the body. 

Kidney changes

You might have some changes in the way your kidneys work. You have regular blood tests to check how well they are working.

Problems peeing

You might have problems with passing urine such as not being able to empty your bladder (retention), finding it hard to pass urine (hesitancy) or passing urine without thinking about it (incontinence). Or you might have the urge to pass urine often.

Let your healthcare team know if that happens.

Tiredness and weakness

You might feel very tired and as though you lack energy.

Various things can help you to reduce tiredness and cope with it, for example exercise. Some research has shown that taking gentle exercise can give you more energy. It is important to balance exercise with resting.

Fluid build up (oedema)

A build up of fluid may cause swelling in your arms, hands, ankles, legs, face and other parts of the body. Contact your healthcare team if this happens to you.

Bone or joint pain

You might experience pain in your bones and joints. Your bones may fracture. Speak to your doctor if you develop problems with your bones.

High levels of a substance called uric acid in your blood

High levels of uric acid in your blood can lead to a build up of crystals in body tissues and cause a type of arthritis known as gout. You’ll have regular blood tests to check these levels.

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). You might have one or more of them. They include:

• not having enough fluid in the body (dehydration). You might not pass much urine or it might be a very dark colour. Your skin might also be very dry or you might feel dizzy

• mood changes may include feeling low (depressed), worried and panicked (anxious), very happy and excited (euphoric), irritable, agitated or having mood swings

• passing out (fainting) – if you feel lightheaded or dizzy make sure you sit or lie down

• changes to your heart or heart rhythm - tests such as a heart trace (ECG) might pick this up. Your heart might also be less able to pump blood around the body

• a build up of fluid in the lungs or in between the layers of tissue surrounding the lungs. You might cough and have shortness of breath

Rare side effects

This happens in fewer than 1 in 100 people (less than 1%). You might have:

• tumour lysis syndrome, causing changes to the levels of substances in your blood due to the breakdown of cancer cells. You may have fluids and medicines to help prevent kidney damage and other side effects, such as changes in your heart's rhythm and seizures (fits)

What else do you need to know?

Other medicines, foods and drink

Cancer drugs can interact with medicines, herbal products, and some food and drinks. We are unable to list all the possible interactions that may happen. An example is grapefruit or grapefruit juice which can increase the side effects of certain drugs.

Tell your healthcare team about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies. Also let them know about any other medical conditions or allergies you may have.

Loss of fertility

It is not known whether this treatment affects ​fertility​ in people. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Pregnancy and contraception

This treatment may harm a baby developing in the womb. It is important not to become pregnant or father a child while you are having treatment. Talk to your doctor or nurse about effective contraception before starting treatment.

Women must not become pregnant for at least 5 weeks after the end of treatment. Men should not father a child for at least 3 months after treatment. 

Breastfeeding

It is not known whether this drug comes through into the breast milk. Doctors usually advise that you don’t breastfeed during this treatment and for 3 days after the final dose.