Targeted and immunotherapy treatment for lung cancer

Targeted cancer drugs work by targeting the differences in cancer cells that help them to grow and survive. Other drugs help the immune system to attack cancer. They are called immunotherapies.

Some drugs work in more than one way. So, they are targeted as well as working with the immune system.

When you might have targeted and immunotherapy drugs for lung cancer

Whether you have targeted therapy or immunotherapy will depend on:

• the type of lung cancer you have
• how far the cancer has grown (the stage)
• treatment you may have already had
• whether your cancer has changes (mutations ) in certain proteins or genes

Non small cell lung cancer (NSCLC)

Targeted therapy – you might have a targeted drug for:

• cancer that has been completely removed with surgery (stage 1B to 3A)

• locally advanced cancer

• metastatic cancer

Immunotherapy – you might have immunotherapy for:

• locally advanced (some stage 3) cancers

• cancer that has spread to another part of the body (metastatic)

Small cell lung cancer

Immunotherapy – you might have immunotherapy for extensive stage disease

Tests on your cancer cells

Doctors look for certain changes in genes (mutations) in your lung cancer that help it to grow and divide. They look for changes in the:

• epidermal growth factor receptor (EGFR) gene

• anaplastic lymphoma kinase (ALK) gene

• ROS1 gene

• mesenchymal-epithelial transition (MET) gene

• RET gene

• KRAS gene

• neurotrophic tyrosine receptor kinase (NTRK) gene

• BRAF V600 gene

They usually test a sample of your lung cancer tissue from when you were first diagnosed. Or from your operation if you had one. 

The results of the tests show whether a targeted cancer drug or immunotherapy is suitable for you.

If your cancer has a particular gene change, your doctor will call it positive for the change. For example, EGFR mutation positive.

There are lots of different targeted cancer drugs and immunotherapy drugs. You usually have one drug on its own. Sometimes you might have it with other treatments, such as chemotherapy. Your doctor will tell you which drug is suitable for you.

Are these drugs available in the UK?

New cancer drugs are licensed for use in a particular way.  For example, a drug might have a license to treat a particular stage or type of lung cancer. 

Once a drug has a license, several independent organisations approve the new cancer drugs before doctors can prescribe them on the NHS.

In England, the National Institute for Health and Care Excellence (NICE) decides which drugs and treatments are available on the NHS.

In Wales, the All Wales Medicines Strategy Group (AWMSG) advises NHS Wales. They generally follow NICE decisions but can also issue their own guidance.

The Scottish Medicines Consortium (SMC) advises NHS Scotland. Its decisions are separate from decisions made by NICE.

Some of the below drugs might not be available throughout the UK. It might depend on where you live whether you can have a certain drug. Your doctor will be able to tell you what drug is available for you.

Targeted drugs for non small cell lung cancer (NSCLC)

EGFR gene changes

Epidermal growth factor receptor (EGFR) is a protein on the surface of cells. It helps the cells to grow and divide. Some cells have a fault in the EGFR gene. This causes it to signal to the cancer cells to divide and make more copies (replicate). 

EGFR inhibitor drugs can block the signal from EGFR. So the cancer cells stop growing. 

If your lung cancer has an EGFR gene change (mutation), your doctor might offer one of the drugs below. They are called tyrosine kinase inhibitors (TKIs). The drug you have may depend on the type of EGFR gene change your cancer has and if you’ve had treatment before.

The following drugs are used for locally advanced and metastatic NSCLC if you haven't had any treatment before. They include:

• gefitinib (Iressa)

• afatinib (Giotrif)

• erlotinib (Tarceva)

• dacomitinib (Vizimpro)

Another EGFR inhibitor drug is Osimertinib (Tagrisso). You might have it:

• for untreated locally advanced or advanced NSCLC
• for stage 1B to 3A NSCLC that has been completely removed with surgery
• with pemtrexed and platinum based chemotherapy for untreated advanced NSCLC

ALK gene changes

About 5 in 100 people (5%) with NSCLC have a change in a gene called anaplastic lymphoma kinase (ALK). This gene change can happen when ALK joins with another gene. The gene change signals the cancer cell to divide and make more copies of itself. 

These drugs are called ALK inhibitors. You usually have one of these drugs as a first treatment for metastatic NSCLC. They include:

• crizotinib (Xalkori)

• ceritinib (Zykadia)

• alectinib (Alcensa)

You may have alectinib also for stage 1B (cancer 4cm or larger) to 3A NSCLC after surgery to completely remove the cancer.

Brigatinib (Alunbrig) and lorlatinib (Lorviqua) are ALK inhibitors that you may have after other treatments stopped working.

ROS1 gene changes

The ROS1 gene change is similar to the ALK gene change. This change means that the cancer receives signals to grow. Some targeted drugs block these signals. The following drugs are used for metastatic NSCLC. They include:

• crizotinib (Xalkori) - you may have it if you haven't had any other ROS1 inhibitors before

• entrectinib (Rozlytrek)

MET gene changes

Some lung cancers have a gene change called a (MET) exon 14 skipping change. A drug that targets this gene change is tepotinib. It is a treatment for metastatic NSCLC.

RET gene fusion

A RET gene fusion means a piece of DNA joins with another gene, and the two parts are joined together (fusion). The fusion leads to uncontrolled growth of cells and cancer. There are different types of RET gene fusions. The type depends on which gene is fused (or joined) with RET.

A drug that targets this change is selpercatinib. It is used for metastatic NSCLC. You may have it if you had treatment before but not with a RET inhibitor.

K-RAS gene changes

Some lung cancers have changes in a gene called K-RAS. The K-RAS gene is important in controlling cell growth. Changes to this gene can lead to cells growing and dividing out of control to form cancers. A drug that targets a specific type of this gene change is called sotorasib (Lumakras).

Sotorasib is a treatment for locally advanced or metastatic NSCLC if your cancer has started to grow again after treatment with platinum based chemotherapy or immunotherapy.

NTRK gene fusion

An NTRK gene fusion happens when a piece of the chromosome containing a gene called NTRK breaks off and joins with a gene on another chromosome. This leads to abnormal proteins called TRK fusion proteins. These proteins may cause cancer cells to grow.

The drugs below target this gene change in people with locally advanced and metastatic NSCLC. They are:

• larotrectinib (Vitrakvi)

• entrectinib (Rozlytrek)

BRAF V600 gene change

The BRAF gene provides instructions for making a protein called B-Raf. This protein is involved in helping cells to grow and divide. A specific gene change in the BRAF gene, known as the V600E mutation, causes a change in the protein's structure. This makes it overactive. Dabrafenib plus trametinib target this change if you have metastatic NSCLC.

Multiple growth factor gene changes

Some drugs bind with several growth factor receptors to stop cancer cells from growing. They are called multi kinase inhibitors.

Nintedanib (Vargatef) is a type of multi kinase inhibitor. It is for people with a type of NSCLC called adenocarcinoma.

Immunotherapy

PD-1 and PD-L1 checkpoint proteins

PD-1 means programmed cell death protein 1, and PD-L1 means programmed cell death ligand 1. They are called checkpoint proteins.

Checkpoint proteins are found on the surface of cells. PD-1 is found on the body's T cells and PD-L1 on normal and often cancer cells.

PD-L1 usually binds with PD-1. When PD-L1 on a cancer cell binds with PD-1, it prevents the T cell from recognising the cell as a cancer cell. The T cell sees it as a normal cell and leaves the cell alone. So, it prevents the T cell from killing the cancer cell.

Blocking the binding of PD-L1 to PD-1 with drugs called immune checkpoint inhibitors allows the T cells to recognise and kill cancer cells. There are two types of checkpoint inhibitors:

• PDL-1 inhibitors

• PD-1 inhibitors

Non small cell lung cancer

Types of PDL-1 inhibitors include:

Durvalumab (Imfinzi)

You might have it after chemoradiotherapy treatment for stage 3 locally advanced NSCLC.

Atezolizumab (Tecentriq)

You might have it:

• after surgery to completely remove the cancer and platinum chemotherapy
• for metastatic NSCLC that has not been treated before
• for locally advanced or metastatic NSCLC after chemotherapy (and targeted treatment if your cancer is EGFR negative or ALK positive)
• with bevacizumab, carboplatin and paclitaxel as a treatmetn for metastatic non squamous cell NSCLC

Types of PD-1 inhibitors include:

Pembrolizumab (Keytruda)

You might have it:

• after surgery for stages 1B to 3A NSCLC
• for metastatic NSCLC that has not been treated before
• for NSCLC that has a high risk of coming back after being completely removed with surgery and after platinum chemotherapy
• for NSCLC that can be removed completely with surgery and that has a high risk of coming back. You may have it before surgery with platinum chemotherapy and then after surgery as a treatment on its own

Nivolumab (Opdivo)

You might have it:

• before surgery (neoadjuvant treatment) if your cancer can be removed with surgery
• for locally advanced or metastatic squamous NSCLC

Small cell lung cancer

Atezolizumab (Tecentriq)

For extensive stage small cell lung cancer, you might have an immunotherapy drug called atezolizumab (Tecentriq). You have it with chemotherapy. So you need to be well enough to have this combination of treatments.

Durvalumab (Imfinzi)

You might have durvalumab with etoposide and either carboplatin or cisplatin chemotherapy for untreated extensive stage small cell lung cancer.

More information

For information about all these drugs and their side effects, go to the individual drug pages.