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 been able to develop newer drugs that specifically target these changes. These targeted drugs work differently from standard chemotherapy (chemo) drugs. 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 lung cancer 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 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 typically not used in patients who are coughing up blood or who are on "blood thinners" such as aspirin or warfarin (Coumadin^®). Most current guidelines do not recommend using bevacizumab in patients with the squamous cell type of lung cancer, because it may lead to serious bleeding in the lungs. However, studies are under way to see if bevacizumab is safe as long as the squamous cell cancer is not located near large blood vessels in the center of the chest.

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 lung cancer 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 lung cancers if initial treatment with chemotherapy is no longer working. Erlotinib may 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 milder than those of typical 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 lung cancer, some doctors may add it to standard chemotherapy as part of first-line treatment.

Cetuximab is not FDA approved for use against lung cancer at this time, although it is approved for use against other cancers, and doctors can prescribe it for use in lung cancer. 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 of cetuximab 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 may include headache, tiredness, fever, and diarrhea.

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 non-small cell lung cancers 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 protein that causes the cells to grow and spread. The new drug crizotinib (Xalkori^®) blocks the abnormal ALK protein. In studies of patients whose lung cancers had this gene change, this drug shrank tumors in about 50% to 60% of patients, even though most of them had already had chemotherapy.

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. In August 2011, this drug was approved by the FDA to treat patients with lung cancers that have the ALK gene change. It is taken twice a day as a pill. This drug helps shrink tumors, but it still is not known if it helps patients live longer, so more studies are needed.