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 lung cancer that:

• can't 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 is not used for small cell lung cancer at this time. The drugs that target molecules in non–small cell lung cancer do not work on the molecules in small cell lung cancer. We need more research to find targeted therapy drugs that are effective against small cell lung cancer.

During diagnosis of non–small cell lung cancer, molecular cell and tissue tests are done to look 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 and whether there are drugs that target that mutation.

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+).

There are different types of EGFR mutations. Cancer cells that don't have EGFR mutations 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 to 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 than chemotherapy in treating the cancer.

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

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

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 wild-type EGFR status. It is offered when the cancer has stopped responding to chemotherapy. Erlotinib may also be offered as maintenance therapy for EGFR+ tumours after chemotherapy has finished.

Afatinib may also be given to people with squamous cell lung cancer, if the cancer has stopped responding to chemotherapy with cisplatin.

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 targeted therapy drug used for T790M mutated non–small cell lung cancer is osimertinib (Tagrisso). If you have been given osimertinib before and the cancer comes back, this drug won't be given to you again.

The EGFR exon 20 insertion mutation happens when a small piece of genetic material gets added (inserted) into the area of the EGFR gene called the exon 20.

Targeted therapy drugs used for other EGFR mutations don't work for the EGFR exon 20 insertion mutation.

Amivantamab (Rybrevant) may be used for stage 3B, stage 3C, stage 4 or recurrent non–small lung cancer with the EGFR exon 20 insertion mutation if it doesn't respond to, or stops responding to, chemotherapy with cisplatin or carboplatin.

Anaplastic lymphoma kinase (ALK) 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 (mutation) in the ALK gene, which causes the cancer cells to grow and spread. Cancer cells that have the ALK mutation are called ALK positive (ALK+).

Drugs that target the change in the ALK gene 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 that is ALK positive is crizotinib (Xalkori). If the cancer stops responding to crizotinib, or if you can't take crizotinib, these targeted therapy drugs may be used:

• ceritinib (Zykadia)

• alectinib (Alecensaro)

• brigatinib (Alunbrig)

Lorlatinib (Lorbrena) may be offered if the cancer no longer responds to crizotinib and another ALK targeted therapy drug.

The ROS1 gene makes a protein that is responsible for signals in cells and in cell growth. Non–small cell lung cancer that has a mutation in this gene is called ROS1 positive (ROS1+).

Crizotinib may be given to people with advanced ROS1-positive non–small cell lung cancer. Entrectinib (Rozlytrek) may be offered for ROS1+ advanced or metastatic non–small cell lung cancer, if you have not been given crizotinib as a treatment.

KRAS G12C is a common genetic mutation found in people with non–small cell lung cancer. A tumour that has the KRAS G12C mutation is called KRAS G12C-positive.

Sotorasib (Lumakras) is a targeted therapy drug that can be used to treat people with advanced or metastatic KRAS G12C-positive non–small cell lung cancer that have received at least one other systemic treatment.

BRAF is a protein that sends signals in cells and helps with cell growth. Changes in the BRAF gene, called BRAF V600E, can be found in higher amounts in some types of lung cancer. Cancer cells that have changes to this gene are called BRAF V600E positive (BRAF V600E+).

A combination of dabrafenib (Tafinlar) and trametinib (Mekinist) may be used to treat non–small cell lung cancer that is BRAF V600E positive.

Mutations in the NTRK gene can cause too much cell growth and lead to abnormal cells and cancer. Sometimes this mutation is found in non–small lung cancer. Cancer cells that have changes to this gene are called TRK fusion positive.

Metastatic non−small cell lung cancer that is TRK fusion positive may be treated with larotrectinib (Vitrakvi).

MET exon 14 skipping mutations (METex 14) is a mutation that has been found in a small number of non–small cell lung cancer tumours.

Tepotinib (Tepmetko) or capmatinib (Tabrecta) may be used in people who have unresectable or metastatic non–small cell lung cancer that has METex 14 mutations.

The RET gene makes a protein that is responsible for signals in cells and in cell growth. A very small number of non–small cell lung cancers have a change in the RET gene. Cancer cells that have changes in the RET gene are called RET–positive. RET–positive non–small cell cancer may be treated with the following targeted drugs, instead of chemotherapy.

Gavreto (pralsetinib) may be given to people with RET-positive unresectable or metastatic non–small cell lung cancer.

Retevmo (selpercatinib) may be offered to people with with metastatic RET-positive non–small cell lung cancer.

Tumours need blood vessels to get 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, Zirabev). 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 and paclitaxel (Taxol). If the cancer responds to the chemotherapy, chemotherapy is continued by itself until the cancer starts to grow again.

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 types of 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
• nausea
• weight gain
• difficulty breathing
• cough
• eye and vision problems, including dry eyes, redness, blurred vision and light sensitivity
• skin problems, including rash, itching or nail changes

EGFR inhibitors may cause these side effects:

• sore mouth
• headache
• sleep problems

ALK inhibitors may cause these side effects:

• pain and cramps in the stomach
• heartburn, indigestion
• peripheral nerve damage
• blood clots
• anemia

Dabrafenib and trametinib may also cause these side effects:

• headache
• fever
• joint pain

Larotrectinib may also cause these side effects:

• peripheral nerve damage
• severe stomach pain or vomiting
• problems with speech or coordination
• dizziness or confusion
• mouth sores

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 (called hand-foot syndrome)

Pralsetinib and selpercatinib may cause these side effects:

• bleeding

• liver problems

• high blood pressure

• heart problems

• lung problems

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.

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

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