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Avastin is the brand name for the anti-cancer medication bevacizumab, which belongs to a group of drugs called monoclonal antibodies. An antibody is a molecule produced by the body in response to a foreign invader or antigen. A monoclonal antibody is created in the laboratory to target and inhibit certain proteins. These agents are very specific for the molecules that they are created against and are therefore called targeted therapies.

Mechanism of action

Bevacizumab (Avastin) is a recombinant humanised monoclonal IgG1 antibody. Monoclonal antibodies recognise and lock on to specific proteins (receptors) that are present on the surface of cancer cells.

Once a monoclonal antibody attaches to the target receptor, it triggers the immune system to attack the cancer cells, which then destroy themselves. The antibody can also prevent the receptor from acting on another protein to stimulate tumor growth, proliferation or angiogenesis (blood vessel formation).

In the case of bevacizumab, the mechanism of action is inhibition of a cell surface protein called vascular endothelial growth factor (VEGF). This VEGF helps tumors to form new blood vessels and blocking VEGF stops the cancer from developing its own blood supply.

This reduces the tumor's supply of oxygen and nutrients, therefore preventing its growth and survival. Starved of vital nutrients, the tumour stops growing and shrinks. Drugs that prevent the growth of blood vessels are termed angiogenesis inhibitors or anti-angiogenics.

Clinical uses

The United States Food and Drugs Administration has approved bevacizumab for the first-line treatment of patients with advanced and metastatic (cancer that has spread to vital organs) carcinoma of the colon or rectum. The therapy can also be used to treat advanced non-small cell lung cancer or advanced cancer of the breast, kidney or bowel. Bevacizumab has also been used successfully in the treatment of eye disorders such as age-related macular degeneration and diabetic retinopathy, where abnormal blood vessel growth in the retina leads to leaky vessels that cause retinal damage.

Mode of administration

Bevacizumab may be given in combination with chemotherapy or when being used to treat kidney cancer, it may be given in combination with interferon. The drug is given as a drip into a vein (infusion) every two or three weeks. Bevacizumab is usually administered over a period of 90 minutes for the first infusion and 60 minutes for the second infusion, with infusions thereafter lasting for about 30 minutes.

Pharmacological properties

The estimated half life (a measure of drug action duration) of bevacizumab is approximately 20 days and the time taken for the drug to reach a steady-state concentration in the blood is around 100 days. The volume of distribution is 46 mL/kg and the drug is eliminated from the body at a rate of 2.75 to 5 mL/kg/day, depending on factors such as body weight, gender and extent or size of the tumor.

Side effects

There are several side effects associated with the use of bevacizumab. Side effects may occur either as a reaction to the infusion or as a response to the drug itself.

Some examples of infusion-related reactions include flu-like symptoms, skin rash, allergy, angioedema and abdominal pain. The drug itself may cause nausea, vomiting, diarrhea, constipation, loss of appetite, weakness, hypertension and mouth ulcers as well as raising the risk of bleeding disorders. Bevacizumab can also decrease the white blood cell count and make patients more susceptible to infection.

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Avastin is the brand name for the anti-cancer medication bevacizumab, which belongs to a group of drugs called monoclonal antibodies. An antibody is a molecule produced by the body in response to a foreign invader or antigen. A monoclonal antibody is created in the laboratory to target and inhibit certain proteins.

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1. What is pertuzumab?
2. How does pertuzumab work?
3. Who might be offered pertuzumab?
4. How is pertuzumab given?
5. How long will I have pertuzumab for?
6. Common side effects of pertuzumab
7. Less common side effects of pertuzumab
8. Blood clots
9. Sex and contraception
10. Travel and vaccinations

1. What is pertuzumab?

Pertuzumab belongs to a group of drugs called monoclonal antibodies. It is a targeted (biological) therapy.

Pertuzumab is the drug's generic or non-branded name. Its brand name is Perjeta.
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2. How does pertuzumab work?

Targeted therapies block the growth and spread of cancer. They target and interfere with processes in the cells that cause cancer to grow.

Some breast cancer cells have a higher than normal level of a protein called HER2 (human epidermal growth factor receptor 2) on their surface. Around 15-20% of invasive breast cancers (breast cancer that has the potential to spread to other parts of the body) have this and are called HER2 positive or HER2+.

When HER2 and other HER proteins pair together, they stimulate the breast cancer cells to grow. Pertuzumab attaches to HER2 and prevents this pairing. It may also help the body's immune system destroy breast cancer cells.

How do I know if my breast cancer is HER2 positive or HER2 negative?

All invasive breast cancers are tested for HER2 levels. This is done in a laboratory on a sample of breast cancer tissue removed during a biopsy or surgery. The results are usually available between one and three weeks later.

There are various tests to measure HER2 levels.
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3. Who might be offered pertuzumab?

Only people with HER2 positive breast cancer will benefit from having pertuzumab. If your cancer is HER2 negative, then pertuzumab will not be of any benefit to you.

Before surgery in primary breast cancer

Primary breast cancer is breast cancer that hasn't spread beyond the breast or the lymph nodes under the arm. Pertuzumab can be given to people with primary breast cancer before surgery (known as neo-adjuvant treatment) for:

Before surgery in locally advanced breast cancer

Locally advanced breast cancer means the breast cancer has spread to the tissues and lymph nodes around the chest, neck and under the breastbone. Pertuzumab can be given to people with locally advanced breast cancer before surgery (known as neo-adjuvant treatment).

After surgery in primary breast cancer (adjuvant treatment)

Pertuzumab can be given after surgery alongside trastuzumab (Herceptin) and chemotherapy to people whose breast cancer has spread to the lymph nodes under the arm.

Secondary and locally advanced breast cancer

Pertuzumab can be used to treat secondary breast cancer (when cancer cells from the breast have spread to other parts of the body such as the bones, lungs, liver or brain).

It's also used for locally advanced breast cancer that can't be removed by surgery.

Pertuzumab is only suitable for people who haven't previously had targeted therapies such as trastuzumab or chemotherapy for secondary or locally advanced breast cancer.

You may also be offered pertuzumab as part of a clinical trial.
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4. How is pertuzumab given?

For primary breast cancer, pertuzumab is given in combination with another targeted therapy called trastuzumab and chemotherapy.

For secondary or locally advanced breast cancer, pertuzumab is given in combination with trastuzumab and a chemotherapy drug called docetaxel.

Pertuzumab is given once every three weeks. It is injected intravenously (into a vein), usually in the hand or arm, although there are other ways of giving it depending on factors such as how easy it is for chemotherapy staff to find suitable veins, and your preferences.

You'll be given your treatment as an outpatient at the hospital. It usually takes between 30 and 60 minutes to have pertuzumab.
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5. How long will I have pertuzumab for?

Before surgery

If you are having pertuzumab before surgery, it's given for three to six cycles alongside trastuzumab and chemotherapy.

After surgery

If you are having pertuzumab after surgery, it's given alongside trastuzumab and chemotherapy for around one year.

Before and after surgery

Some people will have pertuzumab before and after surgery. Up to 18 cycles can be given in total.

Secondary and locally advanced breast cancer

If you're having pertuzumab to treat secondary or locally advanced breast cancer (that can't be removed by surgery) you will continue to have it alongside trastuzumab after the chemotherapy has finished, for as long as the drugs are keeping the cancer under control and you're coping with any side effects.
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6. Common side effects of pertuzumab

Like any drug, pertuzumab can cause side effects. Everyone reacts differently to drugs and some people have more side effects than others. The side effects of pertuzumab can usually be controlled or reduced and those described here will not affect everyone.

This information does not list all the possible side effects. If you have any questions about side effects, whether they are listed below or not, talk to your specialist team.

Because pertuzumab is given alongside other drugs, you may also experience side effects from these. It's sometimes difficult to know which drug causes which side effects because of this. Some of the side effects listed below won't apply if you are having pertuzumab and trastuzumab without chemotherapy.

Find out more about the side effects of trastuzumab and chemotherapy.

Diarrhoea

Tell your specialist or GP if you have diarrhoea as they can prescribe drugs to help. Contact your specialist team if you have four or more episodes of diarrhoea within 24 hours. Drink plenty of fluids to avoid getting dehydrated.

Itchy skin with or without a rash

This can be uncomfortable, but using a moisturiser and sunscreen may help. Your specialist team may suggest drugs such as antihistamines to reduce itching.

Upper respiratory tract infections

These affect the nose, sinuses and throat. You may develop a cough, shortness of breath, headaches, a blocked nose or a sore throat.

Sore mouth

Your specialist team may suggest non-alcohol mouthwashes to help. Use a soft toothbrush and take regular sips of water to keep your mouth moist. Some people need to take strong pain relief to help with the soreness so they can eat and drink.

Increased risk of infection

Having this treatment can affect the number of healthy blood cells in the body. Not having enough white blood cells can increase the risk of getting an infection. When white blood cells fall below a certain level, it's known as neutropenia.

Contact your hospital immediately if:

you have a high temperature (over 37.5°C) or low temperature (under 36°C), or whatever your chemotherapy team has advised

you suddenly feel unwell, even with a normal temperature

you have any symptoms of an infection, for example, a sore throat, a cough, a need to pass urine frequently or feel cold and/or shivery

Anaemia (having too few red blood cells)

If you feel particularly tired, breathless or dizzy, let your specialist team know. A blood transfusion may be necessary during treatment.

Alopecia (hair thinning/loss)

Pertuzumab and trastuzumab don't usually cause people to lose their hair. Any hair loss caused by chemotherapy should be temporary and in most cases your hair will begin to grow back once your chemotherapy treatment has ended.
Read more information about Breast cancer and hair loss "
Fatigue (extreme tiredness)

It's common to feel extremely tired during your treatment. There are different ways of coping and managing fatigue. Speak to your specialist team if you experience fatigue.
Read tips on coping with and managing fatigue "
Nausea and vomiting

You may experience nausea (feeling sick) and vomiting (being sick). Anti-sickness drugs will be prescribed to help with this. If your nausea or sickness is not controlled by these, tell your specialist team as they may be able to change your anti-sickness drugs.

Loss of appetite

You may not feel like eating, especially if you're feeling sick. It might help to eat small meals, regularly.

Joint pain and stiffness

Your muscles and joints may ache, or you might feel stiff. Taking regular pain relief can help. Talk to your specialist team for advice.
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7. Less common side effects of pertuzumab

Infusion-related (allergic) reaction

Some people have a reaction while having pertuzumab or shortly afterwards. Reactions may include a fever (high temperature), feeling sick, shivering, chills, wheezing and an itchy rash. You will be monitored closely during your treatment so that any reaction can be dealt with immediately. If you have any of these symptoms soon after your treatment, contact your specialist team straight away.

Heart problems

Tell your specialist team if you have symptoms such as feeling like your heart is racing, or feeling dizzy or lightheaded. You will have heart tests before starting treatment and regularly throughout to check how your heart is functioning. This could be an echocardiogram (echo) or a multiple-gated acquisition (MUGA). Any problems should stop when the treatment has finished.

Breastfeeding

You'll be advised not to breastfeed during treatment and for a few months afterwards. This is because there's a chance your baby could absorb the drug through your breast milk which could be harmful to them.
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8. Blood clots

People with breast cancer have a higher risk of blood clots such as a deep vein thrombosis (DVT). Their risk is higher because of the cancer itself and some treatments for breast cancer. If the cancer has spread to other parts of the body (secondary breast cancer), this also increases the risk.

People with a DVT are at risk of developing a pulmonary embolism. This is when part of the blood clot breaks away and travels to the lung.

Blood clots can be harmful but are treatable so it's important to report symptoms as soon as possible.

If you experience any of the following symptoms contact your local A&E department, GP or specialist team straight away:

pain, redness/discolouration, heat and swelling of the calf, leg or thigh

swelling, redness or tenderness where a central line is inserted to give chemotherapy, for example in the arm, chest area or up into the neck

shortness of breath

tightness in the chest

unexplained cough (may cough up blood)

Find out more about blood clots "
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9. Sex and contraception

It's important you don't get pregnant when you're having pertuzumab or for a few months afterwards because the drug can harm a developing baby. Use an effective barrier method of contraception, such as condoms.
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10. Travel and vaccinations

Depending on whether or not you are having pertuzumab alongside or following chemotherapy, you may or may not be able to have travel or routine vaccinations. This is because some vaccines are safe to have during chemotherapy, while others are not. If you need a vaccination, talk to your specialist team.
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1. What is pertuzumab? 2. How does pertuzumab work? 3. Who might be offered pertuzumab? 4. How is pertuzumab given? 5. How long will I have pertuzumab for? 6. Common side effects of pertuzumab 7. Less common side effects of pertuzumab 8. Blood clots 9. Sex and contraception 10.

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How  Pertuzumab work and relates with Trastuzumab 

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How  Pertuzumab work and relates with Trastuzumab 

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Cancer: Pertuzumab new anti-HER2 therapy in Breast Cancer

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Mechanism of action of a very recent and promising new therapy in cancer: Pertuzumab which is a monoclonal antibody that inhibits HER2 dimerization and thus cancer progression in association with Trastuzumab (Herceptin). Association website: http://www.efp-online.fr Online education: http://www.invivoveritas.fr

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Most used MABs in breast cancer treatment.

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Most used MABs in breast cancer treatment.

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How MABs work by triggering the immune system.

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Monoclonal antibodies which trigger the immune system to treat cancer - Cancer Research UK

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This video from Cancer Research UK shows how monoclonal antibodies work. Some monoclonal antibodies trigger the immune system to attack and kill cancer cells. Although cancer cells are abnormal, they develop from normal cells so they can be difficult for the immune system to spot.

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Trastuzumab

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Trastuzumab is a targeted cancer drug and is also known by its brand name, Herceptin, Herzuma and Ontruzant.

It is a treatment for cancers that have large amounts of a protein called human epidermal growth factor receptor 2 (HER2), such as:

early breast cancer

advanced breast cancer

advanced stomach cancer

You might have the original drug called Herceptin, or a biosimilar such as Herzuma or Ontruzant. A biosimilar is a very similar copy of the original drug, but it is not exactly the same. Biosimilars undergo strict testing to check they work just as well as the original drug.

How it works

Some breast and stomach cancers have large amounts of human epidermal growth factor receptor 2 (HER2). They are called HER2 positive cancers. HER2 makes the cancer cells grow and divide.

Trastuzumab is a type of targeted cancer drug called a monoclonal antibody. It works by attaching to HER2 so it stops the cancer cells from growing and dividing.

How you have trastuzumab

For breast cancer, you might have trastuzumab as a drip into your bloodstream (intravenously) or as an injection under the skin (subcutaneous). If you have trastuzumab intravenously, you may be able to switch to the subcutaneous injection.

For stomach cancer, you usually have trastuzumab as a drip into your bloodstream.

Into your bloodstream

Each treatment takes between 30 and 90 minutes. You have the first treatment over 90 minutes and your team will check you for any side effects. Depending on the effects you have, the next infusion might be shorter.

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:

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 each time you have treatment.

As an injection under the skin

You might have trastuzumab as an injection under the skin, on the upper, outer part of your leg. The injection takes about 2 to 5 minutes.

It is important that your nurse changes which leg you have your injection in each time, to stop the area getting sore. They will check you for side effects for a few hours after the injection.

When you have trastuzumab

For early breast cancer

You might have trastuzumab alone, or together with chemotherapy. You have it before or after surgery and chemotherapy. You usually have it every week (weekly regimen) or every 3 weeks (3 weekly regimen). This continues for up to a year.

For advanced breast cancer

As the first treatment for breast cancer that has spread, you might have it together with the chemotherapy drugs paclitaxel (Taxol) or docetaxel (Taxotere) or with hormone therapies called aromatase inhibitors.

Trastuzumab is also used as a treatment on its own for people who have had at least 2 types of chemotherapy and where hormone therapy has not worked.

You might have it every week or every 3 weeks.

For advanced stomach cancer

You might have trastuzumab as the first treatment for a type of stomach cancer called adenocarcinoma of the stomach that has spread to other parts of the body. You usually have it together with the chemotherapy drug capecitabine (Xeloda) or with the drugs fluorouracil and cisplatin.

Trastuzumab is also used for cancer that started in the area where the food pipe meets the stomach (gastro oesophageal cancer).

You have it every 3 weeks.

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 will also have a heart trace test (ECG) and a heart scan before you start your treatment. You will have heart tests every few months while you are having trastuzumab and for some time after.

Side effects

We haven't listed all the side effects. It's very unlikely that you will have all of these side effects, but you might have some of them at the same time.

How often and how severe the side effects are can vary from person to person. They also depend on what other treatments you're having. For example, your side effects could be worse if you're also having other drugs or radiotherapy.

When to contact your team

Your doctor, nurse or pharmacist will go through the possible side effects. They will monitor you closely 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.

Common side effects

Each of these effects happens in more than 1 in 10 people (10%). You might have one or more of them. They include:

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

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

Bruising and bleeding

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).

Allergic reaction

This usually happens with the first or second treatment. Symptoms include a skin rash, itching, feeling hot and shivering. Other symptoms include redness of the face, dizziness, a headache, shortness of breath and anxiety.

Joint or muscle pain

You might feel some pain from your muscles and joints. Speak to your doctor or nurse about what painkillers you can take to help with this.

Diarrhoea or constipation

Tell your doctor or nurse if you have diarrhoea or constipation. They can give you medicine to help.

Hot flushes or sweats

We have some tips for coping with hot flushes and the possible treatments for men and women. Talk to your doctor if your hot flushes are hard to cope with. They might be able to prescribe you some medicines.

Heart problems

You may get heart problems, such as angina, heart failure or a heart attack. You will have regular heart checks during and after the treatment. Tell your doctor or nurse straight away if you have any chest pain.

Fatigue

Tiredness and weakness (fatigue) can happen during and after treatment - doing gentle exercises each day can keep your energy up. Don't push yourself, rest when you start to feel tired and ask others for help.

Skin and nail problems

Skin and nail problems include a skin rash, dry skin, itching and darker skin. Your nails may also become brittle, dry, change colour or develop ridges. This usually goes back to normal when you finish treatment.

Mouth sores and ulcers

Mouth sores and ulcers can be painful. Keep your mouth and teeth clean; drink plenty of fluids; avoid acidic foods such as oranges, lemons and grapefruits; chew gum to keep the mouth moist and tell your doctor or nurse if you have ulcers.

Soreness, redness and peeling on hands and feet

The skin on your hands and feet may become sore, red, or may peel. You may also have tingling, numbness, pain and dryness. This is called hand-foot syndrome or palmar plantar syndrome.

Moisturise your skin regularly. Your doctor or nurse will tell you what moisturiser to use.

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 goes back to normal a few weeks after your treatment finishes.

Tummy (abdominal) pain

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

Blood pressure changes

During treatment, your blood pressure may be lower or higher than normal. Tell your nurse if you feel dizzy, faint, or if you have headaches, nosebleeds, blurred or double vision, or shortness of breath. Your blood pressure usually goes back to normal while you are on treatment or when treatment ends.

Eye problems

You might have eye problems including blurred vision, sore, red, itchy, dry eyes (conjunctivitis) or an infection. Tell your doctor or nurse if you have this. They can give you eye drops or other medication to help.

Shaking

You might feel like you are shaking or have tremors.

Headaches and dizziness

Let your doctor or nurse know if you have headaches. They can give you painkillers. Don't drive or operate machinery if you feel dizzy.

Swollen hands and feet

You may have swelling of your hands and legs due to a build up of fluid (oedema).

Loss of appetite

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

Difficulty sleeping

It can help to change a few things about how you try to sleep. Try to go to bed and get up at the same time each day and spend some time relaxing before you go to bed. Some light exercise each day may also help.

Lung problems

You might develop a cough or breathing problems. This could be due to infection, such as pneumonia or inflammation of the lungs (pneumonitis). Let your doctor or nurse know straight away if you suddenly become breathless or develop a cough.

A runny nose

You might have a runny nose while having treatment.

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. Avoiding fatty or fried foods, eating small meals and snacks, drinking plenty of water, and relaxation techniques can all 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 treating it once it has started.

Hair thinning

Your hair may thin but you're unlikely to lose all your hair. This usually starts after your first or second cycle of treatment. It is almost always temporary and your hair will grow back when you finish your treatment.

Flu like symptoms

This can happen a few hours after treatment. It may include headaches, muscle aches (myalgia), a high temperature and shivering. Taking paracetamol every 6 to 8 hours can help.

Occasional side effects

Each of these effects happens in more than 1 in 100 people (1%). You might have one or more of them. They include:

anxiety or depression

changes to the way your kidneys work

shingles

infections such as chest or urine infection

numbness or tingling in fingers and toes

liver problems that are very mild and unlikely to cause symptoms

dry mouth

Rare side effects

Each of these effects happens in fewer than 1 in 100 people (1%). You might have one or more of them.

yellowing of the skin and whites of the eyes

inflammation of the lungs

Coping with side effects

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

Important information

Other medicines, foods and drink

Cancer drugs can interact with some other medicines and herbal products. Tell your doctor or pharmacist about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies.

Pregnancy and contraception

This drug may harm a baby developing in the womb. It is important not to become pregnant or father a child while you are having treatment with this drug and for at least 7 months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment.

Fertility

You may not be able to become pregnant or father a child after treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Men might be able to store sperm before starting treatment. And women might be able to store eggs or ovarian tissue. But these services are not available in every hospital, so you would need to ask your doctor about this.

Breastfeeding

Don't breastfeed during this treatment and for 7 months afterwards. The drug may come through in the breast milk.

Treatment for other conditions

Always tell other doctors, nurses, pharmacists or dentists that you're having this treatment if you need treatment for anything else, including teeth problems.

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 the shingles vaccine (Zostavax).

You can:

have other vaccines, but they might not give you as much protection as usual

have the flu vaccine (as an injection)

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.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray. 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

For further information about this treatment go to the electronic Medicines Compendium (eMC) website.

You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.

iWantGreatCare lets patients leave feedback on their experience of taking a particular drug. The feedback is from individual patients. It is not information, or specialist medical advice, from Cancer Research UK.

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Trastuzumab (Herceptin) | Cancer information | Cancer Research UK

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Trastuzumab is a targeted cancer drug and is also known by its brand name, Herceptin, Herzuma and Ontruzant. It is a treatment for cancers that have large amounts of a protein called human epidermal growth factor receptor 2 (HER2), such as: early breast cancer advanced breast cancer advanced stomach cancer You might have the original drug called Herceptin, or a biosimilar such as Herzuma or Ontruzant.

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Affiliations

¹ Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan. hrmukai@east.ncc.go.jp.

² Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.

³ Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.

⁴ Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

⁵ Oncology Clinical Development Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

⁶ Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

⁷ Institute of Molecular Oncology, Showa University School of Medicine, Tokyo, Japan.

Free PMC article

Free PMC article

Affiliations

¹ Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan. hrmukai@east.ncc.go.jp.

² Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.

³ Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.

⁴ Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

⁵ Oncology Clinical Development Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

⁶ Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

⁷ Institute of Molecular Oncology, Showa University School of Medicine, Tokyo, Japan.

Abstract

Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer. In this open-label, multicenter, dose-escalation, phase Ib study, patients received patritumab 9 or 18 mg/kg plus trastuzumab and paclitaxel at known tolerated doses. Safety and tolerability were assessed based on dose-limiting toxicities and other non-life threatening adverse events. The pharmacokinetic profile for patritumab was determined based on the target trough level. Clinical efficacy was evaluated based on the overall response rate and progression-free survival. Six patients received patritumab 9 mg/kg and 12 received 18 mg/kg. The most common adverse events were diarrhea, alopecia, leukopenia, neutropenia, and maculopapular rash. No dose-limiting toxicities were observed. The target trough serum concentration was achieved in all patients at a dose of 18 mg/kg. Overall response rate was 38.9% and median progression-free survival was 274 days. In conclusion, patritumab plus trastuzumab and paclitaxel was tolerable and efficacious at both doses. We recommend the dose level of 18 mg/kg for future phase II studies. (Clinical trial registration: JapicCTI-121772.).

Keywords: Breast cancer; HER3 protein; human; metastasis; patritumab; trastuzumab.

References

Campbell MR, Amin D, Moasser MM. HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy. Clin Cancer Res 2010; 16: 1373-83. - PMC - PubMed

Gullick WJ. The c‐erbB3/HER3 receptor in human cancer. Cancer Surv 1996; 27: 339-49. - PubMed

Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2: 127-37. - PubMed

Pinkas‐Kramarski R, Soussan L, Waterman H et al Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J 1996; 15: 2452-67. - PMC - PubMed

Bièche I, Onody P, Tozlu S, Driouch K, Vidaud M, Lidereau R. Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer 2003; 106: 758-65. - PubMed

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antineoplastic combined chemotherapy protocols / adverse effects

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antineoplastic combined chemotherapy protocols / therapeutic use*

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national center for biotechnology information

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Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer - PubMed

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Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trast ...

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Abstract

The recent development of monoclonal antibodies targeting growth factor receptors in cancer treatment represents a milestone for both researchers and physicians. Advances in the understanding of key molecular pathways for tumour growth and survival have facilitated the development of these targeted therapies, in particular in breast cancer. This review focuses on the three most important recombinant humanised monoclonal antibodies that have shown activity in women with breast cancer: trastuzumab, pertuzumab and bevacizumab. Trastuzumab, an anti-erbB2 (human epidermal growth factor receptor) monoclonal antibody, is currently routinely used in both the metastatic and adjuvant settings for patients with erbB2-positive tumours. Pertuzumab, a monoclonal antibody binding to a different epitope on erbB2 than trastuzumab, is under early clinical evaluation. This drug has been developed for breast cancer patients, whether overexpressing erbB2 or not. Bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor-A, is being evaluated in the metastatic setting for its antiangiogenic properties, and is showing promising results.

Molecular and Genetic Predictors of Breast-to-Brain Metastasis: Review and Case Presentation.

Medress Z, Hayden Gephart M. Medress Z, et al. Cureus. 2015 Jan 31;7(1):e246. doi: 10.7759/cureus.246. eCollection 2015 Jan. Cureus. 2015. PMID: 26180670 Free PMC article. Review.

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antineoplastic agents / therapeutic use*

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vascular endothelial growth factors / antagonists & inhibitors*

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national center for biotechnology information

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Monoclonal antibody-based targeted therapy in breast cancer: current status and future directions - PubMed

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The recent development of monoclonal antibodies targeting growth factor receptors in cancer treatment represents a milestone for both researchers and physicians. Advances in the understanding of key molecular pathways for tumour growth and survival have facilitated the development of these targeted ...

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Introduction to Monoclonal Antibodies (MABs) and explanation about how do they work.

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Monoclonal antibodies (MABs) are a type of targeted drug therapy. Monoclonal just means all one type. So each MAB is a lot of copies of one type of antibody. They are made in a laboratory.

How they work

MABs work by recognising and finding specific proteins on cancer cells.

Each MAB recognises one particular protein. So different MABs have to be made to target different types of cancer. Depending on the protein they are targeting, they work in different ways to kill the cancer cell or stop it from growing.

Many different MABs are already available to treat cancer. Some are licensed to treat a particular type of cancer while others can be effective against several types. Some newer types are still in clinical trials.

Ask your doctor or specialist nurse if MABs are used to treat your type of cancer and if they are suitable for you.

Types of monoclonal antibody

MABs work in different ways and some work in more than one way. They may do one of the following:

Block signals telling cancer cells to divide

Cancer cells often make large amounts of molecules called growth factor receptors. These sit on the cell surface and send signals to help the cell survive and divide.

Some MABs stop growth factor receptors from working properly, either by blocking the signal or the receptor itself. So the cancer cell no longer receives the signals it needs.

Below is a video showing how MABs work when they stop cancer cells making proteins.

Carry cancer drugs or radiation to cancer cells

Some MABs have drugs or radioactive substances attached to them.

The MAB finds the cancer cells and delivers the drug or radioactive substance directly to them. These are called conjugated MABs.

Below is a video showing how MABs work when they carry cancer drugs or radioactive substances to cells.

Other MABs

Some MABS have an effect on the immune system. The immune system is then in a better position to kill cancer cells. Because MABs work in different ways, some of these drugs are also a type of immunotherapy. Examples of how they do this include:

blocking proteins that stop the immune system working (checkpoint inhibitors)

attaching to cancer cells, making it easier for the cells of the immune system to find them (a process called antibody-dependent cell-mediated cytotoxicity, or ADCC)

How you have them

You have MAB treatment as an injection under the skin (subcutaneous injection), or through a drip (infusion) into a vein. For some drugs, you have your first treatment into your vein, then further treatments as an injection under your skin.

How often you have treatment and how many treatments you need will depend on:

which MAB you have

the type of cancer you have

Testing

Before you have some types of MAB you might need to have tests using some of your cancer cells or a blood sample to find out whether the treatment is likely to work. These tests look for changes in certain proteins or genes.

You cancer specialist can tell you if this applies to your treatment. This is not the case for all MABs and you don't always need this test.

To test your cancer cells, your specialist needs a sample (biopsy) of your cancer. They might be able to test some tissue from a biopsy or operation you have already had.

Examples of MABS

All MABs have names that include 'mab' at the end of their generic name, for example:

trastuzumab (Herceptin)

pertuzumab (Perjeta)

bevacizumab (Avastin)

rituximab (Mabthera)

We haven't listed them all here but you can find more information about these and other MAbs in our list of cancer drugs.

Side effects

All treatments have side effects. These can vary depending on the type of MAB you have. They also depend on whether the MAB has a drug or radioactive substance attached to it.

Allergic reaction during treatment

A common side effect of some MABs is an allergic reaction to the drug. This reaction is most likely to happen during treatment and when you first have the treatment.

If this is possible with your drug, you might have paracetamol, a steroid and an antihistamine drug before treatment to prevent a reaction.

An allergic reaction can include these symptoms, though you may not have all of them:

breathlessness

fever and chills

an itchy rash

flushes and faintness

Your nurse will monitor you and treat any symptoms if they happen.

General side effects

Side effects might include:

skin changes such as red and sore skin or an itchy rash

diarrhoea

tiredness

flu-like symptoms such as chills, fever, dizziness

feeling or being sick

For more information about the side effects of your treatment, go to the individual drug pages.

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Monoclonal antibodies | Targeted cancer drugs | Cancer Research UK

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Monoclonal antibodies (MABs) are a type of targeted drug therapy. Monoclonal just means all one type. So each MAB is a lot of copies of one type of antibody. They are made in a laboratory. MABs work by recognising and finding specific proteins on cancer cells. Each MAB recognises one particular protein.

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How Monoclonal Antibodies work in a cancer cell,