Targeted therapy for non–small cell lung cancer

Some people with non–small cell lung cancer have targeted therapy. It uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. Targeted therapy may also be called molecular targeted therapy.

You may have targeted therapy to treat non–small cell lung cancer that:

• cannot be removed with surgery because it has spread to lymph nodes
• has spread (metastasized) to other parts of the body
• has come back (recurred) after chemotherapy or has not responded to chemotherapy

Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of targeted therapy. You may also receive other treatments.

Targeted therapy drugs used for non–small cell lung cancer

Molecular tissue testing is done during diagnosis of non–small cell lung cancer for different types of changes (called gene mutations) in the cancer cells. The type of targeted therapy you are offered will depend on which gene mutation is found during this testing. People with non–small cell lung cancer that does not have these genetic mutations are not given targeted therapy.

EGFR targeted therapy

Epidermal growth factor receptor (EGFR) is a receptor on the surface of cells that sends signals to cells that allow them to grow and divide. A mutation in the EGFR gene can cause cancer cells to grow and divide more than normal. Cancer cells that have the EGFR mutation are called EGFR positive (EGFR+). Cancer cells that don’t have the EGFR mutation are called wild-type EGFR.

EGFR tyrosine kinase inhibitors (EGFR TKIs) block EGFR from working, which stops or slows the growth of cancer cells. They are taken as pills.

EGFR TKIs are usually given instead of chemotherapy for people who have advanced or metastatic non–small cell lung cancer that is EGFR+. Research has shown that these drugs improve quality of life, increase the amount of time before the cancer starts to grow again and are more effective in treating the cancer.

The following EGFR TKIs are used for EGFR+ non–small cell lung cancers:

• gefitinib (Iressa)
• afatinib (Giotrif)
• erlotinib (Tarceva)

Erlotinib may also be given to people who have had one chemotherapy drug combination for advanced or metastatic non–small cell lung cancer with a positive or unknown EGFR status. It is offered when the cancer has stopped responding to chemotherapy. It may also be offered as maintenance therapy for EGFR+ tumours after chemotherapy has finished.

T790M mutations

EGFR TKIs often shrink tumours and can control non–small cell lung cancer for several months. But over time, the cancer cells develop another mutation in the EGFR gene and the drug stops working. If you have been taking an EGFR TKI and it stops working, your healthcare team may take a sample of another tumour to look for new gene mutations. One of the changes that may be found is called the T790M mutation.

The EGFR TKI that is given to people with advanced or metastatic non–small cell lung cancer that develops the T790M mutation is osimertinib (Tagrisso).

ALK targeted therapy

Anaplastic lymphoma kinase is a protein that helps with cell growth and division. It is controlled by the ALK gene.

A very small number of non–small cell lung cancers have a change (rearrangement) in the ALK gene, which causes the cancer cells to grow and spread. The ALK gene rearrangement is most often seen in non-smokers and light smokers with the adenocarcinoma type of non–small cell lung cancer.

Drugs that target the ALK gene rearrangement are usually given instead of chemotherapy because they are more effective at shrinking the tumours. They are taken as pills.

The targeted therapy drug that is first used to treat advanced or metastatic non–small cell lung cancer with the ALK gene rearrangement is crizotinib (Xalkori) or ceritinib (Zykadia).

If the cancer stops responding to other targeted therapy, alectinib (Alecensaro), brigatinib (Alunbrig) or lorlatinib (Lorbrena) can be used.

ROS1 mutations

Crizotinib may be given to people with advanced non–small cell lung cancer that has the ROS1 gene mutation (ROS1-positive). This mutation is more often seen in younger people or non-smokers and light smokers.

BRAF-V600E mutations

BRAF is a protein that helps with signals in cells and helps cells grow. Lung cancer with the BRAF V600E mutation that has stopped responding to chemotherapy may be treated with a combination of targeted therapy drugs:

• dabrafenib (Tafinlar) and trametinib (Mekinist)

Angiogenesis inhibitors

Tumours need blood vessels to get the nutrients and oxygen to survive and grow. The growth of new blood vessels is called angiogenesis. Angiogenesis inhibitors try to starve a tumour by stopping the development of new blood vessels.

The angiogenesis inhibitor used for advanced or metastatic non–small cell lung cancer is bevacizumab (Avastin, Mvasi). This drug targets the vascular endothelial growth factor (VEGF), which is a protein that helps new blood vessels grow.

Bevacizumab is combined with 2 chemotherapy drugs – carboplatin (Paraplatin, Paraplatin AQ) and paclitaxel (Taxol). If the cancer responds to the chemotherapy, it is continued by itself until the cancer starts to grow again.

Side effects

Side effects can happen with any type of treatment for non–small cell lung cancer, but everyone’s experience is different. Some people have many side effects. Other people have few or none at all.

Targeted therapy attacks cancer cells but doesn’t usually damage healthy cells, so there are usually fewer and less severe side effects than with chemotherapy or radiation therapy. Chemotherapy and radiation therapy can damage healthy cells along with cancer cells.

If you develop side effects, they can happen any time during, immediately after or a few days or weeks after targeted therapy. Sometimes late side effects develop months or years after targeted therapy. Most side effects go away on their own or can be treated, but some side effects may last a long time or become permanent.

Side effects of targeted therapy will depend mainly on the type of drug or combination of drugs, the dose, how it’s given and your overall health. Some common side effects of all targeted therapy for non–small cell lung cancer are:

• flu-like symptoms, such as fever and chills
• fatigue
• diarrhea
• constipation
• low white blood cell count
• loss of appetite
• taste changes
• eye problems, including dry eyes, redness, blurred vision and light sensitivity

EGFR inhibitors may cause these side effects:

• skin problems, including nail changes
• sore mouth
• headache
• sleep problems

ALK inhibitors may cause these side effects:

• pain and cramps in the stomach
• heartburn, indigestion
• tingling and numbness in fingers and toes
• blood clots
• anemia

Bevacizumab may cause these side effects:

• bleeding
• a hole in the intestines (called a bowel perforation)
• high blood pressure
• pain, redness or burning in the hands and feet (hand-foot syndrome)

Tell your healthcare team if you have these side effects or others you think might be from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

Information about specific cancer drugs

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.

Questions to ask about targeted therapy

Find out more about targeted therapy. To make the decisions that are right for you, ask your healthcare team questions about targeted therapy.