Immunotherapy

Immunotherapy is a drug treatment used for some types of lung cancers. Immunotherapy is often shortened to IO (immuno-oncology).

Immunotherapy drugs help the body’s immune system identify, attack and destroy cancer cells whilst leaving healthy cells alone. They can be taken alone or in combination with other treatments.

In this section, we’ll explain:

• How immunotherapy works and when it is used
• What treatments are available for lung cancer
• Receiving immunotherapy
• Potential side effects 
• When treatment ends.

How immunotherapy works

Immunotherapy helps your immune system fight cancer.

T-cells respond to specific proteins on the surface of other cells that tell them what to do. Healthy cells have proteins on their surface that tell T-cells to ignore them. Unhealthy cells don’t have these proteins, so the T-cells know to kill them. 

While cancer cells would ideally be killed by the immune system’s T-cells, some of them have proteins that make them appear like healthy cells so the T-cells don’t kill them. One of these cancer-cell proteins is called PD-L1 (programmed cell death ligand 1). 

When this protein connects with a T-cell protein called PD-1 (programmed cell death protein 1), it convinces the T-cells that it’s a healthy cell, not a cancer cell, and so avoids being destroyed. 

The connection between the PD-1 and PD-L1 proteins is called an immune checkpoint. This checkpoint is known to stop the immune system’s T-cells doing their job of destroying cancer cells.

Immunotherapy drugs block, or inhibit, this checkpoint and so your body’s own T-cells can once again connect with and kill the cancer cells.

When is immunotherapy used to treat lung cancer?

As with any treatment for cancer, decisions about using immunotherapy are based on knowing the type of lung cancer you have, and if it is in one place or it has spread.

Immunotherapy drugs can be used to treat some types of locally advanced or advanced non-small cell lung cancers. Small cell lung cancer has fewer immunotherapy options, though treatments are under development. Some people with previously untreated extensive stage small cell lung cancer may be able to have an immunotherapy treatment in combination with chemotherapy. 

Doctors can’t accurately predict who will respond to immunotherapy or how well, but evidence shows that it may give longer-term positive results for around one in five people. 

For some people, immunotherapy can be effective for several years.

During diagnosis, you should be given a biopsy. The biopsy can check for one of the proteins on the cancer cells – PD-L1. The levels of this protein can help doctors decide if they will offer you immunotherapy.

What immunotherapy drugs are available?

There are currently four main lung cancer immunotherapy drugs available as a standard treatment on the NHS. 

• nivolumab (Opdivo®)
• pembrolizumab (Keytruda®) 
• atezolizumab (Tecentriq®) 
• durvalumab (Imfinzi®)

These are all monoclonal antibodies that are PD-1/PD-L1 checkpoint inhibitors. Nivolumab and pembrolizumab target and block the PD-1 protein on the T-cell, and atezolizumab and durvalumab target and block the PD-L1 protein on the cancer cell.

You may have an immunotherapy drug on its own or in combination with chemotherapy. 

Immunotherapy drugs can be used as your first treatment, known as first-line treatment. Others are used after another drug treatment and would be called a second-line or third-line treatment.

Durvalumab can sometimes be given as an additional (adjuvant) treatment for a year after combined chemotherapy and radiotherapy when the person’s lung cancer is under control. 

Atezolizumab, in combination with carboplatin and etoposide (chemotherapy drugs), may also be used to treat some people with previously untreated, extensive-stage small cell lung cancer, who also have a PS of 0 or 1.

Receiving immunotherapy

Immunotherapy is a systemic cancer treatment that you will receive through an intravenous infusion (drip), like chemotherapy. It is usually an outpatient treatment in a chemotherapy day unit.

Nivolumab and durvalumab are given every two weeks, but sometimes every four weeks to reduce hospital visits. Atezolizumab can be given every three or four weeks, and pembrolizumab every three or six weeks. Your healthcare team will speak to you about your treatment plan.

Treatment normally takes around 90 minutes.

When you arrive for your first appointment, a nurse will take your height and weight to work out your body mass index (BMI). This may be used to calculate the amount of immunotherapy drugs you need. 

They will also check your blood before treatment, and regularly during and after treatment, to see if your white blood cells (cells that fight infection), haemoglobin (cells that carry oxygen), and platelets (cells that clot the blood) are normal. This is called your blood count. 

The blood sample will also check if your blood biochemistry (kidney and liver function) is within normal limits. If your blood count is too low, you might get a blood transfusion, drug dose reduction, or delay in your treatment. 

Your temperature and blood pressure will also be checked so the nurse can be sure you are well enough to get your treatment.

Depending on the drug, there is likely to be a maximum number of treatments you can have (for example, 26 treatments for durvalumab) or a maximum length of time you may be on it (for example, 24 months for nivolumab, pembrolizumab and atezolizumab).

These limits are in place because there is no clear evidence that continuing the treatment will have any benefit compared to stopping after the time limit or number of treatments. 

However, your treatment may stop earlier if your cancer stops responding to it and starts to get worse again, or you have adverse side effects that make it unwise to continue treatment. At this point, your doctors will talk to you about any other available treatment and care options. 

Potential side effects

When being treated with immunotherapy, your immune system will become more active. This can cause side effects such as:

• fatigue (tiredness)
• flu-like symptoms
• rashes 
• diarrhoea
• inflammation (in your lungs, liver, kidneys, thyroid or pituitary gland).

While the side effects can often be milder than what you may expect from chemotherapy, some people can experience severe immune-related side effects, but the more serious side effects occur less often.

How do you know if the treatment is working

With chemotherapy or targeted therapies, effective treatment would show up as a reduction, or no increase, in tumour size. Immunotherapy can be different. Your cancer may appear to grow at the beginning of your treatment. This is called pseudo-progression. It can make it look like your treatment isn’t working but it is a known response to the treatment. 

When immunotherapy treatment works as it should, it encourages more and more immune cells to attack the cancer. The immune cells collect inside and around the tumour making it appear larger on a scan. As treatment progresses, the immune cells can kill the cancer cells, and the tumour can be seen to get smaller.

You may notice yourself that the treatment is working if your symptoms have improved, for example, you are less breathless or not coughing as much. 

Some people do experience a significant health improvement and are able to return to work, do vigorous exercise such as running or get away on a long-overdue holiday.

When treatment ends

If you have reached the end of the treatment plan, it usually means that your lung cancer has continued to respond to the treatment over that time. 

Immunotherapy has the potential to keep your lung cancer at bay so you may not need to have any further treatment at this point. 

This may feel quite scary as it seems like the cancer is no longer being treatment. However, you will receive regular checks from your medical team, perhaps every six to twelve weeks, to make sure your cancer remains stable. 

If any further lung cancer is found, it will be thoroughly investigated, and new treatment options considered depending on the results of these tests.