Lung Cancer (Non-Small Cell)

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Treating Lung Cancer - Non-Small Cell TOPICS

Targeted therapies for non-small cell lung cancer

As researchers have learned more about the changes in lung cancer cells that help them grow, they have developed newer drugs that specifically target these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs. They sometimes work when chemo drugs don’t, and they often have different (and less severe) side effects. At this time, they are most often used for advanced lung cancers, either along with chemo or by themselves.

Drugs that target tumor blood vessel growth (angiogenesis)

For tumors to grow, they must form new blood vessels to keep them nourished. This process is called angiogenesis. Some targeted drugs block this new blood vessel growth.

Bevacizumab (Avastin®): Bevacizumab is a type of drug known as a monoclonal antibody (a man-made version of a specific immune system protein). It targets vascular endothelial growth factor (VEGF), a protein that helps new blood vessels to form.

This drug has been shown to prolong survival of patients with advanced non-small cell lung cancer (NSCLC) when it is added to standard chemotherapy regimens as part of first-line treatment. Bevacizumab is given by infusion into a vein every 2 to 3 weeks. While chemotherapy plus bevacizumab is usually given for 4 to 6 cycles, many doctors continue giving bevacizumab by itself afterward until the cancer starts growing again.

The possible side effects of this drug are different from (and may add to) those of chemotherapy drugs. Some of these effects can be serious.

Bevacizumab can cause serious bleeding, which limits its use to some extent. It is not used in patients who are coughing up blood. Most current guidelines do not recommend using bevacizumab in patients with the squamous cell type of NSCLC, because it may lead to serious bleeding in the lungs.

Other rare but possibly serious side effects include blood clots, holes forming in the intestines, heart problems, and slow wound healing. More common side effects include high blood pressure, tiredness, low white blood cell counts, headaches, mouth sores, loss of appetite, and diarrhea.

Drugs that target EGFR

Epidermal growth factor receptor (EGFR) is a protein found on the surface of cells. It normally helps the cells to grow and divide. Some NSCLC cells have too much EGFR, which causes them to grow faster.

Erlotinib (Tarceva®): Erlotinib is a drug that blocks EGFR from signaling the cell to grow. It has been shown to help keep some lung tumors under control, especially in women and in people who never smoked. It is used by itself, mainly for advanced NSCLC if initial treatment with chemotherapy is no longer working. It can also be used as the first treatment in patients whose cancers have a mutation (change) in the EGFR gene.

This drug is taken daily as a pill. The side effects of erlotinib tend to be different from those of standard chemotherapy drugs. The most worrisome side effect for many people is an acne-like rash on the face and chest, which in some cases can lead to skin infections. Other side effects can include diarrhea, loss of appetite, and feeling tired.

Cetuximab (Erbitux®): Cetuximab is a monoclonal antibody that targets EGFR. For patients with advanced NSCLC, some doctors may add it to standard chemotherapy as part of first-line treatment.

Cetuximab is not FDA approved for use against NSCLC at this time, although it is approved for use against certain other cancers, so doctors can prescribe it for use in NSCLC. This drug is expensive, and not all insurance companies may cover the cost. If you are considering taking this drug, it is important to find out beforehand if your insurance will cover it.

Cetuximab is given by IV infusion, usually once a week. A rare but serious side effect is an allergic reaction during the first infusion, which could cause problems with breathing and low blood pressure. You may be given medicine before treatment to help prevent this. Many people develop skin problems such as an acne-like rash on the face and chest during treatment, which in some cases can lead to infections. Other side effects can include headache, tiredness, fever, and diarrhea.

Afatinib (Gilotrif™): Like erlotinib, afatinib is a drug that blocks the signal from EGFR that tells cells to grow. It was recently approved to be used (without chemotherapy) as the first treatment for advanced NSCLCs that have certain mutations in the EGFR gene.

This drug is taken daily as a pill. Common side effects include skin problems, diarrhea, mouth sores, and loss of appetite. Skin problems include rash, dry skin, and itching.

For more detailed information on the skin problems that can result from anti-EGFR drugs, see our document Targeted Therapy.

Drugs that target the ALK gene

About 5% of NSCLCs have been found to have a rearrangement in a gene called ALK. This change is most often seen in non-smokers (or light smokers) who have the adenocarcinoma subtype of NSCLC. The ALK gene rearrangement produces an abnormal ALK protein that causes the cells to grow and spread.

Crizotinib (Xalkori®) is a drug that blocks the abnormal ALK protein and can shrink tumors in patients whose lung cancers have the ALK gene change. Although it can help after chemotherapy has stopped working, it is now often the first drug used (instead of chemotherapy) in patients whose cancers have the ALK gene rearrangement.

This drug is taken twice a day as a pill. The most common side effects are mild and included nausea and vomiting, diarrhea, constipation, swelling, fatigue, and eye problems. Some side effects can be severe, such as low white blood cell counts, lung inflammation, and heart rhythm problems.

Ceritinib (Zykadia) is a newer drug that targets the abnormal ALK protein. It was recently approved to treat patients after treatment with crizotinib is stopped (either because of side effects or because the drug stopped working).

This drug is taken by mouth, once a day. Common side effects tend to be mild and include nausea, vomiting, diarrhea, constipation, abdominal (belly) pain, fatigue, and decreased appetite. Some serious side effects can also occur, such as liver damage, lung inflammation, and heart rhythm problems.


Last Medical Review: 05/22/2013
Last Revised: 04/30/2014