Targeted therapy

Targeted therapy is a drug treatment that targets specific features of cancer cells to stop the cancer growing and spreading. The drugs circulate through the body like chemotherapy but they work in a more focused way and may have fewer side effects than chemotherapy. However, targeted therapy does not work for all cancer types or all people.

The body constantly makes new cells to help us grow, replace worn-out tissue and heal injuries. Healthy cells multiply and die in an orderly way. Cancer cells are different – they multiply faster and keep growing. This happens because of changes in the genes of the cancer cells.

These gene changes affect the proteins that allow the cancer cells to grow and survive; they also create features within or on the surface of the cancer cells that can be targeted. Each targeted therapy drug acts on a particular feature of the cancer cell. Your doctor may call this the “molecular target”. The drug will only be given if tests show that the cancer cells have the target.

Targeted therapy may kill the cancer cells or slow their growth, causing the signs and symptoms of cancer to reduce or disappear. These drugs often have to be taken long term, but many people continue their usual activities and enjoy a good quality of life.

For some types of cancer, your doctor will test a tissue sample to see if the cells contain a particular target that is allowing the cancer to grow. People with the same cancer type may be offered different treatments based on their test results.

The chance of having cancer cells with a suitable target for a particular targeted therapy may be much higher or lower depending on the type of cancer.

Because each cancer is unique, people may have different treatment plans, even if they have the same type of cancer. The 3 most common cancer treatments are:

• surgery
• chemotherapy
• radiation therapy (also called radiotherapy).

Other treatments used for some types of cancer include:

• targeted therapy
• immunotherapy
• hormone therapy.

Targeted therapy, chemotherapy, immunotherapy and hormone therapy are different types of drug therapy. They are known as systemic treatment because the drugs circulate and kill cancer cells throughout the body.

Cancer treatments may be used on their own or in combination. For example, you may have surgery to remove a tumour, followed by targeted therapy to stop the cancer returning.  Sometimes, targeted therapy is combined with chemotherapy. Doctors will recommend the best treatment for you based on the type and stage of cancer, its genetic make-up, your age and your general health.

Using targeted therapy to treat cancer has improved survival rates for several types of cancer, and many people respond well. However, targeted therapy is not an option for everyone with cancer.

In Australia, targeted therapy drugs are now available for a range of cancers, including blood cancers such as leukaemia and lymphoma; common cancers such as bowel, breast, lung and melanoma; and other cancers such as cervical, head and neck, kidney, liver, ovarian, sarcoma, stomach and thyroid.

For most of these cancers, targeted therapy is available only when the cancer is advanced. For some types, however, it may also be available for early-stage cancer to improve the chance of a good outcome.

New drugs are becoming available all the time. Talk to your doctor about the latest options. Targeted therapy may be used:

• before surgery to reduce the size of a cancer (neoadjuvant therapy)
• after surgery to destroy any remaining cancer cells (adjuvant therapy)
• to treat cancer after initial treatments if the cancer has come back (recurrent disease) or hasn’t responded to other treatments
• as initial treatment for advanced cancer that has certain gene changes
• as long-term treatment to try to prevent the cancer coming back or growing (called maintenance treatment).

Most targeted therapy drugs are not safe to use during pregnancy or while breastfeeding. Ask your doctor for advice about contraception. If you may want to have children in the future, talk to your doctor about your options (e.g. storing sperm or eggs) before starting targeted therapy. If you become pregnant while taking targeted therapy, let your medical team know immediately.

Targeted therapy and chemotherapy are both types of systemic treatment, but they work in different ways.

Chemotherapy drugs affect all cells that multiply quickly. This means the drugs can kill cancer cells and also damage other cells that multiply quickly, such as healthy cells in the mouth, stomach, bone marrow or hair. This is why chemotherapy side effects may include mouth ulcers, nausea, low numbers of blood cells (leading to infections or anaemia) and hair loss.

Targeted therapy drugs focus on the cancer cells, while limiting damage to healthy cells. Many people experience fewer side effects with targeted therapy. Some side effects, however, can be serious. Sometimes, the target is on healthy cells as well as cancer cells, and this can lead to particular side effects. For example, the EGFR gene may be on healthy skin cells as well as the cancer cells, so the targeted therapy can cause a rash.

The cancer must contain the particular target or the drug won’t work. The response to targeted therapy varies widely. In some cancers, 4 out of 5 people assessed as suitable for a particular targeted therapy drug will respond. For other cancers, the rate of success is much lower. This is due to a range of factors, including how many of the cancer cells carry the target.

Cancer cells can eventually stop responding to a targeted therapy drug even if it works at first. If this happens, you may be offered another targeted therapy drug or a different type of treatment. Less commonly, a targeted therapy drug may cause serious side effects and the treatment plan will need to be adjusted (e.g. a lower dose or different drug may be tried).

Ask your cancer specialist if there is a suitable targeted therapy for you. This will depend on the type and stage of the cancer. Your specialist may also need to test the cancer to see if one of the currently available drugs is an option. If you have not already had surgery or a biopsy, you may need to have a biopsy so a tissue sample can be collected.

Many more targeted therapy and other new drugs are being studied in clinical trials. Talk with your specialist about the latest developments and whether there are any trials that might be right for you.

Download our booklet ‘Understanding Clinical Trials and Research’

Targeted therapy is usually prescribed by a medical oncologist or haematologist. It may be given on its own or combined with chemotherapy or other types of cancer drugs.

Some targeted therapy drugs are given in repeating cycles, with rest periods in between. Others are taken every day without any breaks.

Cancer treatments are usually given in line with protocols that set out which drugs to have, how much and how often. Your specialist may need to adjust the protocols to your individual situation. You can find information about protocols for targeted therapy and other cancer drugs at eviQ.

Targeted therapy is given in different ways:

• as tablets or capsules that you can swallow
• as an intravenous (IV) infusion into a vein, either through a drip in your arm or into a port (a small device inserted under the skin of the chest or arm)
• as an injection under the skin.

When targeted therapy is given as an infusion, some people react to the infusion process (e.g. skin rashes, nausea, difficulty breathing). Reactions can occur during the infusion or several hours afterwards. You will be monitored and may be given medicines to help prevent this.  Reactions are more common with the first couple of infusions, so they may be given at a `slower rate than later treatments.

How long you have targeted therapy depends on the aim of the treatment, how the cancer responds and any side effects you may have. In many cases, targeted therapy tablets or capsules need to be taken daily for many months or even years. Your treatment team can give you more details.

In some cases, you may need to take special precautions to protect other people in your household while you are having targeted therapy. Talk to your doctor about any safety measures that you may need to take.

The Pharmaceutical Benefits Scheme (PBS) covers most of the cost of many prescription medicines, including some targeted therapy drugs. Medicines not on the PBS are usually expensive, but you may be able to receive them as part of a clinical trial or at a reduced cost through a compassionate access program.

You will have regular check-ups with your doctor, blood tests and different types of scans to see whether the cancer has responded to treatment with targeted therapy.

A good response from targeted therapy will make a cancer shrink or even disappear completely from scans. In some cases, the cancer remains stable, which means it doesn’t grow in size on scans, but also does not shrink or disappear.

People with stable disease can live for a long time and have a good quality of life.

These drugs reduce the blood supply to a tumour to slow or stop it growing. They target various proteins linked with the growth of new blood vessels and stop them from working. An example is bevacizumab.

High levels of the protein HER2 cause cancer cells to grow uncontrollably. Some targeted therapy drugs destroy the HER2 positive cancer cells, or reduce their ability to divide and grow. Examples include trastuzumab and pertuzumab.

These drugs target a protein called CD20 found on some B-cell leukaemias and non-Hodgkin lymphomas. Examples include rituximab and obinutuzumab.

A monoclonal antibody is linked with a chemotherapy drug using a linking protein. These drugs target the cancer with a high dose of chemotherapy without damaging healthy cells. Examples include trastuzumab emtansine and trastuzumab deruxtecan.

Tyrosine kinase inhibitors (TKIs) block proteins called tyrosine kinases from sending signals that tell cancer cells to grow, multiply and spread. Without this signal, the cancer cells may die. Examples include osimertinib, sunitinib, imatinib, dasatinib and lorlatinib

These drugs block mammalian target of rapamycin (mTOR), a protein that tells cancer cells to grow and spread. An example is everolimus.

These drugs block poly (ADP-ribose) polymerase (PARP), a protein that repairs damaged DNA in cancer cells. An example is olaparib.

These drugs block cyclin-dependent kinase (CDK) from sending signals that tell cancer cells to grow, multiply and spread. Without this signal, the cancer cells may die. Examples include palbociclib, ribociclib and abemaciclib.