Lung Cancer: Targeted Therapy

What is targeted therapy?

Targeted therapy uses medicines that act on specific parts of cancer cells that help the cancer grow and spread. Targeted therapy can sometimes be more helpful than standard chemotherapy (chemo). Sometimes it works when chemo doesn't. Because targeted therapy is focused on the cancer cells, it may cause less harm to normal cells. But these medicines do cause side effects. 

When might targeted therapy be used for lung cancer?

Targeted therapy can be used to treat advanced forms of non-small cell lung cancer (NSCLC). These are bigger tumors that have spread from where they first started in the lung. They might also be used after surgery for smaller (stage I) tumors. They might be used alone or along with other treatments.

So far, no targeted therapy medicines have been shown to help treat small cell lung cancer (SCLC).

Most targeted therapies are only helpful if the cancer cells have certain gene changes. So if you have NSCLC, your healthcare provider will have lab tests done on your cancer cells to look for certain proteins and gene changes. This helps your provider know if and which targeted therapy medicine might work for you.

Types of targeted therapy for non-small cell lung cancer

EGFR inhibitors

Some targeted therapy medicines aim for a protein on cells called the epidermal growth factor receptor (EGFR). Sometimes NSCLC cells have too much EGFR. This makes them grow faster. Blocking EGFR stops these signals and can keep the cancer cell from growing.

These are some of the medicines that can be used if your lung cancer cells have certain EGFR gene changes (mutations):

• Erlotinib

• Afatinib

• Gefitinib

• Osimertinib

• Dacomitinib

All of these medicines are taken as pills.

Necitumumab is an EGFR inhibitor that can be used in people with the squamous cell sub-type of NSCLC. This medicine is given by IV (intravenous) infusion into a vein.

Angiogenesis inhibitors

Some targeted therapy medicines target new blood vessel growth. This process is called angiogenesis. Tumors need new blood vessels to grow. So keeping the tumors from making new blood vessels can help keep them from growing. These medicines are often used along with chemotherapy for more advanced NSCLC:

• Bevacizumab

• Ramucirumab

These medicines are given by IVIV. They go right into your blood through a vein.

ALK inhibitors

A small number of NSCLCs have changes in the ALK gene. This change makes an abnormal ALK protein that causes the cancer cells to grow and spread. Medicines that target the abnormal ALK protein can often help shrink tumors. They're often used instead of chemo. They might also be used if chemo stops working. ALK inhibitors include:

• Crizotinib

• Ceritinib

• Alectinib

• Brigatinib

• Lorlatinib

These medicines are all taken as pills.

Other treatment targets

Scientists have found other gene and protein changes in NSCLC cells that can be the focus of targeted therapy. These cancer cell changes are less common, but if they're found, targeted therapy can be used.

ROS1 gene changes

Changes in the ROS1 gene are most often found in people with the NSCLC subtype called adenocarcinoma. These cancer cells usually don't have ALK or EGFR mutations. Medicines that target abnormal ROS1 include:

• Crizotinib

• Ceritinib

• Lorlatinib

• Entrectinib

All of these are taken as pills.

BRAF gene changes

Changes in the BRAF gene allow cancer cells to make an altered BRAF protein that helps them grow and spread.

Dabrafenib and trametinib may be used together to treat NSCLCs with a certain kind of BRAF gene mutation. These medicines are taken as pills.

RET fusion gene changes

Abnormal RET proteins are made when the RET fusion is changed. This leads to out-of-control cancer cells growth.

RET inhibitors include:

• Selpercatinib

• Pralsetinib

• Cabozantinib

• Vandetanib

They attack the RET protein to slow cancer cell growth. They're taken as pills.

MET gene changes

MET gene changes cause cancer cells to make abnormal MET proteins that help them grow and spread.

Capmatinib and tepotinib are MET inhibitors. They attack the MET protein. They're taken as pills.

NTRK fusion gene changes

Changes in NTRK fusion can cause cancer cell growth.

Larotrectinib and entrectinib target and damage the proteins made by the NTRK genes. These medicines are taken as pills.

HER2 gene changes

Human epidermal growth factor receptor 2 can help some cancers grow.

The medicine trastuzumab deruxtecan may be used to target HER2 mutations. It is given by IV infusion.

Possible side effects of targeted therapy

You may have side effects from your treatment. The possible side effects can vary a great deal depending on which medicine you are getting. 

Side effects of  EGFR inhibitors can include: 

• Acne-like rash on the face and chest

• Nausea

• Mouth sores

• Diarrhea

Common side effects of  angiogenesis inhibitors  include:

• High blood pressure

• Feeling tired

• Diarrhea

• Headache

• Bleeding

• Low white blood cell counts. (This means you have a higher risk for infections).

Less common, but more serious side effects include:

• Severe bleeding

• Blood clots

• Holes in the intestines

• Heart problems

• Slow wound healing

Common side effects of  ALK inhibitors include:

• Nausea and vomiting

• Bowel problems (diarrhea or constipation)

• Feeling tired

• Eye problems or vision changes

Common side effects of ROS1 inhibitors include:

• Dizziness

• Bowel problems (diarrhea or constipation)

• Feeling tired

• Vision changes

Side effects of medicines that target BRAF gene changes include:

• Skin changes, like thickening, rashes, itching, and sun sensitivity

• Hair loss

• Fever

• Joint pain

• Headaches

• Nausea

• Diarrhea

• Feeling tired

RET inhibitor side effects include:

• Dry mouth

• Bowel problems (diarrhea or constipation)

• High blood pressure

• Feeling tired

• Rashes

• Muscle and joint pain

• Swelling in the hands and/or feet

• High blood sugar

• Changes in blood counts

Common MET inhibitor side effects include:

• Swelling in the hands, feet, or both

• Feeling tired and weak

• Loss of appetite

• Nausea and vomiting

• Bowel problems (diarrhea or constipation)

• Changes in blood counts

Side effects of medicines that target NTRK gene change s include:

• Tiredness

• Dizziness

• Nausea and vomiting

• Bowel problems (diarrhea or constipation)

• Weight gain

Side effects of medicines that target HER2 gene changes include:

• Low blood counts

• Nausea

• Vomiting

• Fatigue

• Hair loss

• Loss of appetite

• Heart or lung problems

Working with your healthcare provider

It's important to know which targeted therapy medicines you're taking. Write down the names of your medicines. Ask your healthcare team how they work and what side effects they might cause. Tell them about any changes you notice so they can help you control them. Most side effects can be treated, and there may be ways to keep them from getting worse.

Talk with your healthcare providers about what signs to look for and when to call them. Make sure you know what number to call with questions. Is there a different number for evenings, holidays, and weekends?

It may be helpful to keep a diary of your side effects. A written list will make it easier for you to remember your questions when you go to your appointments. It will also make it easier for you to work with your healthcare team to make a plan to manage your side effects.