Atezolizumab and bevacizumab

Atezolizumab and bevacizumab are cancer drugs. How to pronounce the drug names are in brackets:

• atezolizumab (a-teh-zoh-liz-yoo-mab)

• bevacizumab (bev-a-ciz-oo-mab)

You have this combination for locally advanced or metastatic hepatocellular carcinoma (HCC). HCC is a type of primary liver cancer. Your doctor may suggest this treatment if:

• surgery was not successful, or you can’t have surgery
• you haven’t had systemic treatment before

Whether you can have this treatment will also depend on:

• your level of activity – you need to be able to do most things apart from heavy physical work

• how well your liver is working – your liver needs to be class A in the Child-Pugh classification system

How do atezolizumab and bevacizumab work?

Atezolizumab is a type of immunotherapy called a monoclonal antibody. It works by binding to PD-L1 proteins on the surface of cancer cells. This stops cancer cells from suppressing the immune system. The immune system can then find and kill the cancer cells.

Bevacizumab is a targeted cancer drug called an angiogenesis inhibitor. It targets a cancer cell protein called vascular endothelial growth factor (VEGF). This protein helps cancers grow blood vessels so they can get food and oxygen from the blood. All cancers need a blood supply to survive and grow.

Bevacizumab blocks this protein and stops the cancer from growing blood vessels, so it can't grow.

How do you have atezolizumab and bevacizumab?

You have atezolizumab as an injection under the skin (subcutaneously) or as a drip into your bloodstream (intravenously). You have bevacizumab as a drip into your bloodstream.

Injection under your skin (subcutaneous injection)

You usually have injections under the skin (subcutaneous injection) into the thigh.

You might have stinging or a dull ache for a short time after this type of injection but they don't usually hurt much. The skin in the area may go red and itchy for a while.

Into your bloodstream

You might have treatment through a long plastic tube that goes into a large vein in your chest. The tube stays in place throughout the course of treatment. This can be a:

• central line
• PICC line
• portacath

If you don't have a central line

You might have treatment through a thin short tube (a cannula) that goes into a vein in your arm. You have a new cannula each time you have treatment.

How often do you have atezolizumab and bevacizumab?

You have atezolizumab and bevacizumab as cycles of treatment. This means that you have the drugs and then a rest to allow your body to recover.

The length of each cycle is usually 21 days (3 weeks). You continue taking atezolizumab and bevacizumab for as long as the treatment is working and you are not experiencing too many side effects.

If you have atezolizumab as an injection under the skin

You have each cycle of treatment in the following way:

You then start your next cycle of treatment.

If you have atezolizumab as a drip into the bloodstream

You have each cycle of treatment in the following way:

You then start your next cycle of treatment.

Tests

You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver and kidneys are working.

You might also have blood pressure and urine checks.

What are the side effects of atezolizumab and bevacizumab?

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, headaches, feeling cold and shivery and generally 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. 

Breathlessness and looking pale

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

Bruising, bleeding gums or nosebleeds

This is due to a drop in the number of platelets in your blood. These blood cells help the blood to clot when we cut ourselves. You may have nosebleeds or bleeding gums after brushing your teeth. Or you may have lots of tiny red spots or bruises on your arms or legs (known as petechiae).

Less commonly, you may have bleeding elsewhere in the body, such as in the lung. Symptoms include coughing up blood. Let your healthcare team know if this happens and go to Accident and Emergency (A&E).

Changes to levels of thyroid hormones

The level of your thyroid hormones may drop (hypothyroidism). You may feel tired or cold, gain weight, feel sad or depressed, or your voice may deepen. You will have regular blood tests to check your thyroid hormone levels.

Less commonly, you may have high levels of thyroid hormones (hyperthyroidism). You may lose weight or feel hot, anxious or hyperactive.

Loss of appetite

You might lose your appetite for various reasons while having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

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. 

Headaches

Let your doctor or nurse know if you have headaches. They can give you painkillers such as paracetamol to help.

High blood pressure

Tell your doctor or nurse if you have headaches, nosebleeds, blurred or double vision or shortness of breath. You have your blood pressure checked regularly.

Rarely, a very high blood pressure might be life threatening needing immediate medical treatment. Symptoms include a headache, feeling and being sick, loss of eyesight, seizures and loss of consciousness.

Shortness of breath, a cough, and nose and throat inflammation

This treatment may affect your breathing, cause a cough, a sore throat, or a blocked or runny nose.

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. It might help to avoid fatty or fried foods, eat small meals and snacks and take regular sips of water. Relaxation techniques might also help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is easier to prevent sickness rather than treat it once it has started.

Diarrhoea or constipation

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

Skin changes

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

Other skin changes include blisters, inflamed skin, skin shedding, cracked skin and inflamed hair follicles.

Rarely, you may have a severe skin reaction that may start as tender red patches which leads to peeling or blistering of the skin. You might also feel feverish and your eyes may be more sensitive to light. This is serious and could be life threatening.

Or you may have psoriasis, causing flaky patches of skin which form scales.

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.

Hair loss

You could lose all your hair. This includes your eyelashes, eyebrows, underarms, legs and sometimes pubic hair. Your hair will usually grow back once treatment has finished but it is likely to be softer. It may grow back a different colour or be curlier than before. Some people may have permanent hair loss although this is rare.

Back, muscle, bone and joint pain

You may get pain in your back, muscles, bones and joints.

Tell your doctor or nurse so they can give you painkillers and advice on what to do to help ease the pain.

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.

Swollen hands and feet

Swelling of hands and feet is due to fluid build up. This is called oedema. Let your doctor or nurse know if you have any swelling.

Changes to levels of minerals

You may have low levels of minerals such as magnesium and sodium in your blood. You will have regular blood tests to check for this.

Less commonly, you may have low levels of potassium.

Difficulty speaking

This treatment may cause difficulty speaking because it affects the muscles for speech.

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.

Watery eyes

Watery eyes is also called excessive tearing or epiphora (pronounced ep-if-or-ah). Tell your doctor or nurse if this is a problem for you. They can prescribe medicines to help. Try to avoid dust, pollen or animal hairs as they can make the watering worse. 

Blood clots

Blood clots can develop in the deep veins of your body, usually the leg. This is called deep vein thrombosis (DVT). A blood clot can be very serious if it travels to your lungs (pulmonary embolism), although this isn’t common.

Symptoms of a blood clot include:

•    pain, redness and swelling around the area where the clot is and may feel warm to touch
•    breathlessness
•    pain in your chest or upper back – dial 999 if you have chest pain
•    coughing up blood

A sore mouth

You might get a sore mouth and mouth ulcers. It may be painful to swallow drinks or food. You will have mouth washes to keep your mouth healthy.

You can have painkillers to reduce the soreness. Take them half an hour before meals to make eating easier.

Tummy pain

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

Digestive system changes

You may have bleeding from your bottom (rectum). This may appear as bright red blood in your poo (stools) or on toilet paper. Contact your healthcare team straight away if you have this.

Less commonly, you may develop problems such as a blockage (obstruction) in your gut, a tear in the bowel wall or your bowel may stop working. You may have pain in your bottom due to spasms.

Wound healing problems

This treatment can slow wound healing. If you need to have an operation you may need to stop taking it for a while beforehand. Your doctor will let you know when you can start taking it again.

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.

Ovaries stop working

The ovaries may stop working in pre menopausal women and periods may stop. This may only be temporary and may go back to normal once you stop treatment. But some women might have an early menopause and this treatment could cause infertility.  

Weight loss

You might lose weight while having this treatment. Let your doctor or nurse know and they can recommend ways of maintaining your weight. Or they can refer you to a dietitian.

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:

• an allergic reaction that can cause a rash, shortness of breath, redness or swelling of the face and dizziness. Some allergic reactions can be life threatening. Tell your nurse or doctor if you notice any of these symptoms
• feeling dizzy or fainting
• a hoarse voice
• changes to how your liver works – you will have regular blood tests to check this
• not enough fluid in your body (dehydration) – symptoms may include feeling thirsty, peeing less, dark coloured or strong smelling pee, or feeling very tired
• a stroke – symptoms include a dropped face on one side, weakness and numbness in an arm, slurred speech or difficulty understanding others
• feeling drowsy or sleepy
• the heart not being able to pump blood around the body properly – symptoms may include breathlessness, tiredness, feeling faint or swollen ankles and legs, or a change to your heart rhythm. Rarely, you may have heart changes that affect the layers around the heart, which may interfere with how well the heart works - symptoms may include chest pain, a high temperature, breathlessness or a fast heartbeat
• low levels of oxygen in your body tissues – symptoms may include confusion, restlessness, difficulty breathing, a fast heart beat and bluish skin
• an abnormal connection developing between internal organs and skin or other tissues. This is called a fistula. Your team will explain what symptoms to look out for
• pain in the area between the hip bones (pelvis)

Rare side effects

These side effects happen in fewer than 1 in 100 people (fewer than 1%). You might have one or more of them. They include:

• inflammation of the pituitary gland . Symptoms can include headaches and changes to your vision such as loss or double vision. Contact your healthcare team if you have this
• coeliac disease – a condition that causes damage to the gut when you eat gluten. Gluten is a protein in wheat, barley and rye. Symptoms include diarrhoea, tummy pain and bloating
• weakness or lack of movement on one or both sides of your face (facial paresis)

Other side effects

There isn't enough information to work out how often these side effects might happen. You might have one or more of them. They include:

• high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension) – symptoms may include breathlessness, tiredness, feeling faint or dizzy, chest pain, a fast heartbeat, or swelling in the body legs, ankles, feet and tummy

• a stomach ulcer – symptoms may include tummy pain, indigestion or heartburn. Contact your healthcare team straight away if you have dark, sticky, tarry poos (stools)

• damage of bone tissue in your jaw – symptoms may include pain, swelling or gum infections, or exposed bone in the mouth along either the top or bottom jaws

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do you need to know?

Other medicines, food 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. If this treatment causes early menopause in pre menopausal women, this will mean they can’t have children. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Contraception and pregnancy

This treatment may or may not harm a baby developing in the womb. It is important not to become pregnant or get someone pregnant while you are having treatment. Let your team know straight away if you or your partner become pregnant while having treatment.

Talk to your doctor or nurse about effective contraception you can use during treatment. Ask how long you should use it before starting treatment and after treatment has finished.

Breastfeeding

Don’t breastfeed during this treatment and for 6 months afterwards. The drug may come through in the breast milk.

Other conditions

If you are having tests or treatment for anything else, always mention your cancer treatment. For example, if you are visiting your dentist.

Immunisations

Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and one of the shingles vaccines called Zostavax.

You can have:

• other vaccines, but they might not give you as much protection as usual
• the flu vaccine (as an injection)
• the coronavirus (COVID-19) vaccine - talk to your doctor or pharmacist about the best time to have it in relation to your cancer treatment

Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system recovers from treatment.

Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy.

More information about this treatment

We haven't listed all the very rare side effects of this treatment. For further information see the electronic Medicines Compendium (eMC) website.

You can report any side effect you have that isn’t listed here to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.