Targeted therapies are cancer treatments that stop or slow the spread of cancer by interfering with specific molecules that are involved in the cancer cell’s growth processes. Chemotherapy focuses on cells that divide and grow quickly, which includes cancer cells but also includes other healthy cells in the body, like cells in the digestive tract, hair, bone marrow, and blood, causing multiple side effects. Targeted therapy focuses on other specific features of cancer cells, in an effort to provide treatment for cancer that does less damage to normal cells and causes fewer side effects.1,2
Targeted therapy is also different from chemotherapy in the way it affects cancer cells. Targeted therapies are generally cytostatic, meaning they block the growth or spread of cancer cells. Chemotherapy drugs are cytotoxic, meaning they kill cancer cells.2 There are different categories of targeted therapy that have been developed to treat non-small cell lung cancer (NSCLC). These are based on the genetic mutations and molecular processes that have been found in some NSCLC tumors.
Epidermal Growth Factor Receptor (EGFR)
It is estimated that 10% of patients with NSCLC in the United States have a tumor mutation associated with EGFR. When functioning normally, the EGFR gene helps cells respond to their environment and can trigger cell growth, division, and survival. The EGFR mutations are most often found in tumors in female patients who have never smoked (patients are considered “never smokers” if they have smoked less than 100 cigarettes in their lifetime). The tumors are likely to be adenocarcinoma. However, EGFR mutations are not only found in this type of NSCLC or non-smokers – mutations have also been found in smokers and in other tumor types. Several EGFR inhibitor drugs have been developed to target this specific mutation in NSCLC tumors, including Gilotrif® (afatinib), Iressa® (gefitinib), Portrazza® (necitumumab), Tagrisso® (osimertinib), and Tarceva® (erlotinib).2,3
Anaplastic Lymphoma Kinase (ALK)
An estimated 3-5% of lung tumors have mutations on the ALK gene. When working normally, the ALK gene plays an important role in cell growth, division, and maturation. ALK mutations are more common in light smokers (defined as less than 10 pack years*) and/or never-smokers. These mutations are also associated with younger patient age and adenocarcinomas. Targeted therapies for NSCLC that are ALK inhibitors include Alecensa® (alectinib), Xalkori® (crizotinib), and Zykadia® (ceritinib).2-4
Monoclonal Antibodies and Angiogenesis Inhibitors
Antibodies are a normal part of the immune system that attach to antigens (such as germs) to mark them for destruction by the immune system. Monoclonal antibodies are created in a laboratory to attach to specific antigens on the surface of cancer cells. Monoclonal antibodies used to treat some NSCLC include Avastin® (bevacizumab) and Cyramza® (ramucirumab). These drugs work by targeting molecules that lead to the development of new blood vessels, or angiogenesis. By blocking angiogenesis, these therapies help lessen the blood supply to the tumors and can slow the cancer’s growth. Portrazza (necitumumab), mentioned above, is also considered a monoclonal antibody.1,2
Targeted therapies can cause side effects. Side effects are dependent on the type and dosage of the drugs given. Some common side effects include:
- Skin problems, including rashes, dry skin, and nail changes
- Problems with blood clotting and wound healing
- High blood pressure
- Gastrointestinal perforation (a rare side effect that causes a hole in the intestines)2
Some of the side effects have been linked to better patient outcomes, or better response to treatment. For example, patients who experience a rash that looks like acne while being treated with Tarceva or Iressa (EGFR inhibitors) often have tumors that respond better to these drugs, as compared to patients who do not experience the rash. Another example is seen in patients receiving Avastin (angiogenesis inhibitor). Patients who experience high blood pressure while taking Avastin generally have tumors that respond better to treatment, as compared to patients who do not develop high blood pressure.2
*Pack years is a term used to help quantify the equivalent of how many years a patient has smoked. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. For example, smoking one pack per day for one year equals 1 pack year, whereas smoking two packs per day for two years equals 4 pack years.