Checkpoint Inhibitors

Checkpoint inhibitors are a type of immunotherapy. They are a treatment for cancers such as melanoma skin cancer and lung cancer.

These drugs block different checkpoint proteins. You might also hear them named after these checkpoint proteins – for example, CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors. 

Examples of checkpoint inhibitors include pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo) and atezolizumab (Tecentriq).

What are checkpoint inhibitors?

Checkpoint inhibitors are a type of immunotherapy. They block proteins that stop the immune system from attacking the cancer cells.

Cancer drugs do not always fit easily into a certain type of treatment. This is because some drugs work in more than one way and belong to more than one group.

Checkpoint inhibitors are also described as a type of monoclonal antibody or targeted treatment.

How do checkpoint inhibitors work?

Our immune system protects us from disease, killing bacteria and viruses. One main type of immune cell that does this is called a T cell.

T cells have proteins on them that turn on an immune response and other proteins that turn it off. These are called checkpoint proteins.

Some checkpoint proteins help tell T cells to become active, for example when an infection is present. But if T cells are active for too long, or react to things they shouldn’t, they can start to destroy healthy cells and tissues. So other checkpoints help tell T cells to switch off.

Some cancer cells make high levels of proteins. These can switch off T cells, when they should really be attacking the cancer cells. So the cancer cells are pushing a stop button on the immune system. And the T cells can no longer recognise and kill cancer cells.

Drugs that block checkpoint proteins are called checkpoint inhibitors. They stop the proteins on the cancer cells from pushing the stop button. This turns the immune system back on and the T cells are able to find and attack the cancer cells.

Types

These drugs block different checkpoint proteins including:

• CTLA-4 (cytotoxic T lymphocyte associated protein 4)
• PD-1 (programmed cell death protein 1)
• PD-L1 (programmed cell death ligand 1)

CTLA-4 and PD-1 are found on T cells. PD-L1 are on cancer cells.

PD-1

Checkpoint inhibitors that block PD-1 include:

• nivolumab (Opdivo)
• pembrolizumab (Keytruda)

Nivolumab and pembrolizumab are treatments for some people with:

• melanoma skin cancer
• Hodgkin lymphoma
• non small cell lung cancer

Nivolumab is also a treatment for some kidney cancers and head and neck cancers. And pembrolizumab is used for cancers of the urinary tract.

The urinary tract includes the:

• centre of the kidney (renal pelvis)
• tubes that take urine from the kidneys to the bladder (ureters)
• bladder
• tube that drains urine from the bladder and out of the body (urethra)

CTLA-4

Ipilimumab (Yervoy) is a checkpoint inhibitor drug that blocks CTLA-4. It is a treatment for advanced melanoma and advanced renal cell cancer.

PD-L1

Checkpoint inhibitors that block PD-L1 include:

• atezolizumab
• avelumab
• durvalumab

Atezolizumab is a treatment for:

• lung cancer
• some liver cancers
• some breast cancers
• cancer of the urinary tract (urothelial cancer)

The urinary tract includes the:

• centre of the kidney (renal pelvis)
• tubes that take urine from the kidneys to the bladder (ureters)
• bladder
• tube that drains urine from the bladder and out of the body (urethra)

Avelumab is a treatment for a type of skin cancer called merkel cell carcinoma (MCC) that has spread to other parts of the body. It is also a treatment for some cancers of the urinary tract (urothelial cancers).

Durvalumab is a treatment for non small cell lung cancer (NSCLC).

When you might have these drugs

Ask your doctor if these drugs are suitable for you. Whether you can have this treatment depends on your type of cancer. It might also depend on:

• the stage of your cancer
• whether you have already had certain treatments

To find out if you can have pembrolizumab for non small cell lung cancer, you need to have your cancer cells tested. To have this PD-1 inhibitor for lung cancer, you need to have large amounts of the PD-L1 protein on your cancer cells. This is called PD-L1 positive cancer.  

This testing does not apply to all checkpoint inhibitors. Your doctor or specialist nurse can tell you if this applies to you.

You might be offered checkpoint inhibitors as part of a clinical trial. Or you could ask your doctor whether there are any trials that you could take part in.

How you have treatment

You usually have these drugs as a treatment through a drip into your bloodstream.

Side effects

These drugs boost all the immune cells, not just the ones that target cancer. So the overactive T cells can cause possible side effects. These might include:

• tiredness (fatigue)
• feeling or being sick 
• dry, itchy skin, skin rash   
• loss of appetite
• diarrhoea  
• breathlessness and a dry cough, caused by inflammation of the lungs 

These drugs can also disrupt the normal working of the liver, kidneys and hormone making glands (such as the thyroid). You have regular blood tests to check for this.

Some of these side effects can be serious. Your medical team will talk through the possible side effects so you know what to look out for. Tell your doctor or nurse if you have any side effects so they can treat them as soon as possible. 

Side effects, such as diarrhoea, can be serious. You are also likely to have worse side effects if you have ipilimumab and nivolumab together. You might have these 2 drugs if you have advanced melanoma or advanced renal cell cancer.