Targeted Therapies

Targeted therapy is used to treat non-small cell mutation driven lung cancers, such as ALK+, EGFR+ and ROS1. 

In this page, we’ll cover:

• When a targeted therapy is used to treat lung cancer
• Types of targeted therapy
• Targeted therapy for different mutations, including ALK+ and EGFR+
• Side effects
• What happens if the targeted therapy stops working.

A targeted therapy is a drug that has been designed to block the processes that causes cancer to grow. The drug focuses on, or targets, the mutation, hence why it is called ‘targeted’ therapy. These drugs are also sometimes called biological therapies.

Targeted therapy drugs come as a tablet which you take by mouth every day at home. You do not need to go to hospital to receive this treatment.

When is a targeted therapy used to treat lung cancer

A targeted therapy may be offered to you if:

• Your lung cancer is inoperable or not otherwise radically treatable (treated with an intent to cure), also called advanced lung cancer 
• You have previously had surgery, and your lung cancer has come back
• You have just had surgery for early-stage non-small cell lung cancer that has tested positive for an EGFR mutation (adjuvant treatment)
• Tests on a biopsy have shown that you have a type of lung cancer that may respond well to it 
• Your cancer team thinks it is right for you.

To find out if a targeted therapy may be suitable for you, doctors will have to test some of your cancer cells. This is called a biopsy. Testing the cancer cells for mutations is known as molecular analysis or biomarker testing.

Biopsy tissue is first used to identify the type of lung cancer and then the lung cancer sub-types. Biomarker testing is then carried out on remaining tissue. Occasionally, a further biopsy may be needed to provide the necessary tissue sample.

Find out more about biopsies and genomic testing >>

Types of targeted therapy

The type of targeted therapy you can have will depend on different factors:

• The type of lung cancer you have
• If you have had any other treatments
• Your general health and fitness.

There are currently 8 types of genetically mutated lung cancers that currently have targeted therapy treatment options:

• ALK+ (anaplastic lymphoma kinase)
• BRAF (B-Raf proto-oncogene, serine/threonine kinase)
• EGFR+ (epidermal growth factor receptor)
• KRAS (Kirsten RAt Sarcoma virus)
• MET (mesenchymal-epithelial transition factor)
• NTRK (neurotrophic tropomyosin-related kinase)
• RET (rearranged during transfection)
• ROS1 (relating to the gene c-ros oncogene 1).

There are other known targets, including HER2 for example, but there are currently no licensed treatments for those targets.

For each mutation type, there are different targeted therapy drugs that work best. Your cancer doctor will speak to you about your treatment options and which drugs may be most suitable for you that are available to you.

Targeted therapies for ALK mutation

There are currently five drugs approved for treating ALK positive lung cancer:

• Alectinib (brand name Alecensa®)
• Brigatinib (brand name Alunbrig®)
• Ceritinib (brand name Zykadia®)
• Crizotinib (brand name Xalkori®) 
• Lorlatinib (brand name Lorviqua®).

If you are starting treatment, you may receive any of these drugs for your first-line treatment, though less so crizotinib nowadays as other newer drugs may be considered more useful.

Subsequent lines of treatment may vary. Brigatinib and ceritinib may be second line after crizotinib, followed by third line lorlatinib. 

Lorlatinib may be second-line after alectinib, brigatinib or ceritinib. After these lines of treatment, you may be offered chemotherapy, immunotherapy or a combination of both.

Targeted therapies for BRAF mutation

There is currently one drug combination that may be available under the Cancer Drugs Fund for treating BRAF positive lung cancer:

• Dabrafenib (brand name Tafinlar®) with Trametinib (brand name Mekinist®).

You may receive dabrafenib as your first-line treatment or after other treatments.

Targeted therapies for EGFR mutation

There are currently six drugs approved for treating EGFR positive lung cancer:

• Afatinib (brand name Giotrif®)
• Dacomitinib (brand name Vizimpro®)
• Erlotinib (brand name Tarceva®)
• Gefitinib (brand name Iressa®) 
• Mobocertinib (brand name Exkivity®) 
• Osimertinib (brand name Tagrisso®).

The EGFR mutation type has variations that will determine which targeted therapy you may be offered. Most common are exon 19 deletion or exon 21 L858 mutation, and rarely exon 20 insertion.

The first five drugs may be available as first-line treatments, and osimertinib may be offered as a second line treatment following afatinib, dacomitinib, erlotinib or gefitinib if the treatment has stopped working and your lung cancer tests positive for the T790M mutation. 

For some people with certain rare EGFR mutations, afatinib or erlotinib may be offered as second-line treatment after chemotherapy.

Mobocertinib may be offered to you, following chemotherapy, if your locally advanced or metastatic NSCLC has tested positive for the EGFR mutation with the exon 20 insertion. 

Osimertinib may be offered to some people after surgery, whose lung cancer tests positive for an EGFR mutation, usually for a maximum of three years.

Subsequent treatments may include chemotherapy or immunotherapy, or a combination of both.

Targeted therapies for KRAS mutation

There are currently two drugs that may be used to treat KRAS G12C positive lung cancer:

• Adagrasib (brand name Krazati®) 
• Sotorasib (brand name Lumykras®)

At the moment, testing positive for KRAS G12C mutation positive lung cancer doesn’t mean you will get adagrasib or sotorasib (under the European Access to Medicines Scheme) as your first line treatment. 

They are currently given for previously treated KRAS G12C lung cancer, following one or more lines of chemotherapy or a combination of chemotherapy and immunotherapy.

Targeted therapies for MET exon 14 skipping mutation

There are currently two drugs that may be available to treat MET positive lung cancer: 

• Capmatenib (brand name Tabrecta®)
• Tepotinib (brand name Tepmetko®)

You may receive capmetinib or tepotinib as a first-line treatment. However, even if you test positive for MET exon 14 skipping, you may be offered other treatments before it, such as surgery, radiotherapy, chemotherapy, immunotherapy or a combination of treatments.

If your lung cancer then stops responding to other treatments, you may be able to start on capmetinib or tepotinib.

Targeted therapies for NTRK mutation

There are currently two drugs that can be used to treat NTRK positive lung cancer:

• Entrectinib (brand name Rozlytrek®)
• Larotrectinib (brand name Vitrakvi®).

At the moment, testing positive for NTRK mutation positive lung cancer doesn’t mean you will get these drugs as your first line treatment.

They are currently given for previously treated NTRK+ lung cancer, following one or more lines of chemotherapy or a combination of chemotherapy and immunotherapy

Targeted therapies for RET mutation

There are currently two drugs that may be used to treat RET positive lung cancer: 

• Selpercatinib (brand name Retsevmo®)
• Pralsetinib (brand name Gavreto®)

At the moment, testing positive for RET mutation positive lung cancer doesn’t mean you will get pralsetinib or selpercatinib as your first line treatment. They are currently given for previously treated RET+ lung cancer, following one or more lines of chemotherapy or a combination of chemotherapy and immunotherapy.

Targeted therapies for ROS1 mutation

There are currently two drugs that may be used to treat ROS1 positive lung cancer: 

• Crizotinib (brand name Xalkori®) 
• Entrectinib (brand name Rozlytrek®).

Both of these drugs may be offered to you as your first line treatment if your lung cancer tests positive for the ROS1 mutation. Second and subsequent line treatments would likely be chemotherapy, immunotherapy or a combination of both.

Common side effects 

All forms of cancer treatment have side effects of one sort or another and most people experience some side effects with a targeted therapy.

Side effects tend to be more difficult at the start of treatment. Over time, your body may adapt to the treatment and the side effects can reduce.

Side effects can include:

• Diarrhoea
• Nail infections (paronychia)
• Feeling nauseous or being sick
• Rash or other skin problems

If you are experiencing any of these symptoms, speak to your lung cancer nurse specialist or your medical team.

Severe side effects

You need to contact your lung cancer team for urgent advice if you notice any of these side effects:

• Breathing difficulties, shortness of breath or worsening breathing problems 
• A cough 
• A high temperature (37.5C or higher) 
• Chest pain 
• Slow pulse (50 beats per minute or less), feeling tired, dizzy or faint, or losing consciousness
• Abdominal (belly) pain
• Back pain
• Itching 
• Yellowing of the skin and eyes 
• Changes in mental processes such as confusion, memory loss, and reduced ability to concentrate 
• Changes in mood including irritability and mood swings 
• Changes in speech including difficulty speaking, such as slurred or slow speech.

What happens if the targeted therapy stops working

Over time, targeted therapies can lose their effectiveness. The cancer cells can develop a resistance to the drugs and start to grow again, and this represents one of the main challenges to effective treatment. Your targeted therapy treatment may stop at this point.

For some people who have an isolated recurrence of their lung cancer, it may be treated with surgery or radiotherapy allowing their targeted therapy treatment to restart or continue.

If your cancer develops resistance and your treatment does stop, your cancer doctor will be able to tell you about other treatments that may be available to you.