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As researchers have learned more about the changes in non-small cell lung cancer (NSCLC) cells that help them grow, they have developed drugs to specifically target these changes. Targeted drugs work differently from standard chemotherapy (chemo) drugs. They sometimes work when chemo drugs don’t, and they often have different side effects. At this time, targeted drugs are most often used for advanced lung cancers, either along with chemo or by themselves.
For tumors to grow, they need to form new blood vessels to keep them nourished. This process is called angiogenesis. Some targeted drugs, called angiogenesis inhibitors, block this new blood vessel growth:
Either of these drugs might also be used along with the targeted drug erlotinib (see below) as the first treatment in people whose cancer cells have certain EGFR gene mutations.
Common side effects of these drugs include:
Rare but possibly serious side effects can include blood clots, severe bleeding, holes (called perforations) in the intestine, heart problems, and slow wound healing. If a hole forms in the intestine it can lead to severe infection and may require surgery to fix.
Because of the risks of bleeding, these drugs typically aren’t used in people who are coughing up blood or who are taking drugs called blood thinners. The risk of serious bleeding in the lungs is higher in patients with the squamous cell type of NSCLC, which is why current guidelines do not recommend using bevacizumab in people with this type of lung cancer.
Some NSCLCs have changes in the KRAS gene that cause them to make an abnormal form of the KRAS protein. This abnormal protein helps the cancer cells grow and spread.
About 1 in 8 people (13%) with NSCLC have a specific type of KRAS gene change called a KRAS G12C mutation. NSCLCs with this mutation are often resistant to other targeted drugs such as EGFR inhibitors (see below).
Sotorasib (Lumakras) and adagrasib (Krazati) are drugs known as KRAS inhibitors. They work by attaching to the KRAS G12C protein, which helps keep cancer cells from growing. One of these drugs may be helpful if you have advanced NSCLC, your blood or cancer tissue is tested and the cancer cells are found to have the KRAS G12C mutation, and you've already had at least one other type of drug treatment.
These drugs are taken as pills, typically once or twice a day.
Common side effects can include:
Less common but more serious side effects can include liver damage as well as inflammation (swelling) or scarring in the lungs, which can make it hard to breathe.
Epidermal growth factor receptor (EGFR) is a protein on the surface of cells. It normally helps the cells grow and divide. Sometimes NSCLC cells have too much EGFR, which makes them grow faster.
Drugs called EGFR inhibitors can block the signal from EGFR that tells the cells to grow. Some of these drugs can be used to treat NSCLC.
For advanced NSCLC: One of these drugs is often used as the first treatment for advanced NSCLCs that have certain mutations in the EGFR gene. Most of these drugs are used alone, although erlotinib can also be used along with a targeted drug that affects new blood vessel growth (see above).
For earlier stage NSCLC: Osimertinib can also be used as an adjuvant (additional) treatment after surgery for some earlier stage lung cancers with certain EGFR gene mutations.
All of these medicines are taken as pills.
EGFR inhibitors can often shrink tumors for several months or more. But eventually these drugs stop working for most people, usually because the cancer cells develop another mutation in the EGFR gene. One such mutation is known as T790M.
Osimertinib (Tagrisso) is an EGFR inhibitor that often works against cells with the T790M mutation.
Doctors now commonly get another biopsy when other EGFR inhibitors have stopped working to see if the patient's tumor has developed the T790M mutation (and therefore if this drug might be helpful).
While the EGFR inhibitors listed above can help many people whose cancer cells have EGFR gene mutations, they don’t help everyone. For example, cancer cells with an EGFR gene change known as an exon 20 insertion mutation are much less likely to affected by these drugs.
However, other drugs that target cancer cells with an exon 20 mutation are now available.
Amivantamab (Rybrevant) is a monoclonal antibody (a lab-made version of a specific immune system protein) that targets two proteins that help cancer cells grow: EGFR and MET. Because it binds to two proteins, it’s called a bispecific antibody. This drug is given as an infusion into a vein (IV).
Mobocertinib (Exkivity) is a drug that targets the EGFR protein in a slightly different way. This drug is taken as pills, typically once a day.
These drugs can be used to treat advanced NSCLC when the cancer cells have an exon 20 mutation, typically after chemotherapy has been tried.
Necitumumab (Portrazza) is a monoclonal antibody (a lab-made version of an immune system protein) that targets EGFR. It can be used with chemotherapy as the first treatment in people with advanced squamous cell NSCLC. This drug is given as an infusion into a vein (IV).
Common side effects of all EGFR inhibitors include:
Skin problems can include an acne-like rash on the face and chest, which in some cases can lead to skin infections.
Some of these drugs can also cause more serious, but less common, side effects. For example:
About 5% of NSCLCs have a rearrangement in a gene called ALK. This change is often seen in people who don't smoke (or people who are light smokers) who are younger and who have the adenocarcinoma subtype of NSCLC. The ALK gene rearrangement produces an abnormal ALK protein that causes the cells to grow and spread. Drugs that target the abnormal ALK protein include:
These drugs can often shrink tumors in people whose advanced lung cancers have an ALK gene change. Although they can help after chemo has stopped working, they are often used instead of chemo in people whose cancers have an ALK gene rearrangement.
These drugs are taken as pills.
Common side effects of ALK inhibitors include:
Other side effects are also possible with some of these drugs. Some side effects can be severe, such as inflammation (swelling) in the lungs or other parts of the body, liver damage, nerve damage (peripheral neuropathy), and heart rhythm problems.
About 1% to 2% of NSCLCs have a rearrangement in a gene called ROS1. This change is most often seen in people who have the adenocarcinoma subtype of NSCLC and whose tumors are also negative for ALK, KRAS and EGFR mutations. The ROS1 gene rearrangement is similar to the ALK gene rearrangement, and some drugs can work on cells with either ALK or ROS1 gene changes. Drugs that target the abnormal ROS1 protein include:
These drugs can often shrink tumors in people whose advanced lung cancers have a ROS1 gene change. Crizotinib or ceritinib might be used as first treatment, instead of chemo, and lorlatinib may be used when crizotinib or ceritinib have stopped working. Entrectinib can be used in people with metastatic NSCLC that has a ROS1 gene change.
These drugs are taken as pills.
Common side effects of ROS1 inhibitors include:
Other side effects are also possible with some of these drugs. Some side effects can be severe, such as inflammation (swelling) in the lungs or other parts of the body, liver damage, nerve damage (peripheral neuropathy), and heart problems.
In some NSCLCs, the cells have changes in the BRAF gene. Cells with these changes make an altered BRAF protein that helps them grow. Some drugs target this and related proteins:
These drugs can be used together to treat metastatic NSCLC if it has a certain type of BRAF gene change.
These drugs are taken as pills or capsules each day.
Common side effects can include skin thickening, rash, itching, sensitivity to the sun, headache, fever, joint pain, fatigue, hair loss, nausea, and diarrhea.
Less common but serious side effects can include bleeding, heart rhythm problems, liver or kidney problems, lung problems, severe allergic reactions, severe skin or eye problems, and increased blood sugar levels.
Some people treated with these drugs develop skin cancers, especially squamous cell skin cancers. Your doctor will want to check your skin often during treatment and for several months after. You should also let your doctor know right away if you notice any new growths or abnormal areas on your skin.
In a small percentage of NSCLCs, the cells have certain changes in the RET gene that cause them to make an abnormal form of the RET protein. This abnormal protein helps the cells grow.
Selpercatinib (Retevmo) and pralsetinib (Gavreto) are drugs known as RET inhibitors. They work by attacking the RET protein. These drugs can be used to treat advanced NSCLC if the cancer cells have certain types of RET gene changes.
These drugs are taken by mouth as capsules, typically once or twice a day.
Common side effects can include:
Less common but more serious side effects can include liver damage, lung damage, allergic reactions, changes in heart rhythm, bleeding easily, and problems with wound healing.
In some NSCLCs, the cells have changes in the MET gene that cause them to make an abnormal form of the MET protein. This abnormal protein helps the cells grow and spread.
Capmatinib (Tabrecta) and tepotinib (Tepmetko) are types of drugs known as a MET inhibitors. They work by attacking the MET protein. These drugs can be used to treat metastatic NSCLC if the cancer cells have certain types of MET gene changes.
Capmatinib is taken as pills, typically twice a day. Tepotinib is also taken as pills, but usually once a day.
Common side effects can include:
Less common but more serious side effects can include inflammation (swelling) or scarring in the lungs, which can make it hard to breathe, as well as liver damage.
Some people might become more sensitive to sunlight (or other sources of UV rays) while being treated with capmatinib, so it’s important to protect yourself during treatment (for example, by using sunscreen or wearing clothes that cover your skin).
In a small percentage of NSCLCs, the cancer cells have certain changes in the HER2 gene that help them grow.
Trastuzumab deruxtecan (Enhertu) is a type of medicine known as an antibody-drug conjugate (ADC). It’s composed of a lab-made antibody that targets the HER2 protein, which is linked to a chemotherapy drug. The antibody acts like a homing signal by attaching to the HER2 protein on cancer cells, bringing the chemo directly to them.
This drug can be used to treat NSCLC that can’t be removed by surgery or that has spread, if the cancer cells have certain types of HER2 gene changes, and if at least one other drug treatment has already been tried.
This drug is infused into a vein (IV). It is typically given once every 3 weeks.
This drug can cause low blood cell counts, which can increase a person’s risk of infections and bleeding.
Other common side effects can include nausea, vomiting, diarrhea or constipation, loss of appetite, fever, feeling tired, and hair loss.
This drug can cause serious lung disease in some people, which might even be life threatening. It’s very important to let your doctor or nurse know right away if you’re having symptoms such as coughing, wheezing, trouble breathing, or fever.
This drug can also rarely cause heart damage. Before and during treatment with this drug, your doctor may test your heart function with an echocardiogram or a MUGA scan.
A very small number of NSCLCs have changes in one of the NTRK genes. Cells with these gene changes can lead to abnormal cell growth and cancer. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) target and disable the proteins made by the NTRK genes. These drugs can be used in people with advanced lung cancer that is still growing despite other treatments and whose tumor has an NTRK gene change.
These drugs are taken as pills, once or twice daily.
Common side effects include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea.
Less common but serious side effects can include abnormal liver tests, heart problems, and confusion.
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Last Revised: December 13, 2022