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Developments in Therapy for Non–Small-Cell Lung Cancer

June 2016 Vol 2 No 3

Lung cancer is the second most common cancer in men and women. Approximately 224,390 new cases of lung cancer will be diagnosed in 2016. Lung cancer kills more Americans each year than any other cancer.

Smoking is the most common risk factor for lung cancer, but lung cancer can also be found in people who don’t smoke.

Lung cancer is divided into 2 main types: (1) small-cell lung cancer, and (2) non–small-cell lung cancer, which is referred to as NSCLC.

Small-cell lung cancer affects approximately 10% to 15% of all lung cancers, and smoking is almost always the cause.

NSCLC is the most common type of lung cancer, accounting for approximately 85% to 90% of all cases.

NSCLC is divided into 3 main subtypes, including adenocarcinoma, squamous-cell carcinoma, and large-cell carcino-ma. It is important to know your type of lung cancer, because the treatment for lung cancer differs depending on the specific type.

Genetic Changes

Certain genetic changes (mutations) have been found in patients with NSCLC that can affect the response to different drugs. Therefore, genetic screening is important to identify patients who would benefit most from a specific drug. Genetic screening typically involves removing a small portion of tumor (biopsy) to see whether it contains specific mutations.

Currently, the 2 best-known types of genetic mutations in patients with NSCLC are called EGFR mutations and ALK mutations. Other mutations, including KRAS and VEGF, have also been linked to NSCLC, and more are being currently studied.

In the past few years, new types of drugs have improved survival for patients with lung cancer. The new drugs include:

  1. Immunotherapy for NSCLC
  2. Drugs that target specific mutations in patients with lung cancer and are called targeted drugs

Immunotherapy for NSCLC

Immunotherapies are a new type of drugs for patients with NSCLC that use the patient’s immune system to attack the cancer cells. A healthy immune system attacks abnormal cells and uses what is known as immune checkpoints. PD-1 is a checkpoint protein on the immune cells that keeps immune cells from attacking normal cells in the body by attaching to the PD-L1 (another protein). Some cancer cells have large amounts of PD-L1, which helps them to escape the body’s attack on the cancer cells. New drugs known as immune checkpoint inhibitors target the PD-L1 cellular pathing and help to destroy cancer cells.

Last year, the first 2 drugs that target PD-L1 in NSCLC were approved by the FDA for patients with NSCLC, especially those with PD-1/PD-L1:

  • Opdivo (nivolumab) was approved in 2015 and is used for patients with squamous and nonsquamous metastatic NSCLC (lung cancer that has spread) whose disease worsened with chemotherapy.
    Opdivo works by using the body’s immune system to attack PD-L1 found on cancer cells. By blocking these proteins, Opdivo helps to destroy cancer cells in NSCLC. Opdivo has been shown to improve survival especially among patients with NSCLC with PD-L1.
  • Keytruda (pembrolizumab) was also approved in 2015 for patients with metastatic NSCLC whose tumors express PD-L1 and whose disease worsened during or after chemotherapy. The use of Keytruda was shown to shrink the tumor in patients with NSCLC and PD-L1. Keytruda is prescribed for patients who had a test to verify that their tumor expresses PD-L1.

Targeted Drugs for EGFR Mutations

Targeted drugs are used for patients with a specific mutation; therefore, patients have to be tested for these mutations before they are prescribed these drugs. Many of these drugs have a specific test that can determine if their lung cancer cells include that mutation.

Tarceva (erlotinib), Gilotrif (afatinib), and Iressa (gefitinib) are used for first-line treatment of patients with advanced (metastatic) NSCLC who have EGFR mutations.

Tagrisso (osimertinib) was approved in late 2015 and is the first treatment currently available for patients with metastatic NSCLC plus an EGFR T790M mutation. New evidence suggests that Tagrisso may also work for patients who were just diagnosed with this type of lung cancer (first-line treatment).

Portrazza (necitumumab) is an EGFR inhibitor approved in 2015 for use with 2 other drugs (gemcitabine and cisplatin) for first-line treatment of metastatic squamous-cell NSCLC.

Targeted Drugs for ALK Mutations

Xalkori (crizotinib) was first approved for patients with metastatic NSCLC plus ALK mutations. In 2016, Xalkori was approved for use in patients with metastatic NSCLC and ROS1 mutations. It can therefore be prescribed for patients with NSCLC and either type of mutation.

Zykadia (ceritinib) was approved in 2014 and Alecensa (alectinib) was approved in 2015 for patients with metastatic NSCLC with ALK mutations.

Another drug approved in 2014 for NSCLC is Cyramza (ramucirumab), which is used for patients with squamous NSCLC whose cancer worsened after platinum-based chemotherapy. It is used with docetaxel, another type of chemotherapy, and it does not target any specific mutation. It works by inhibiting the growth of blood vessels (which feed tumors).

Talk to Your Doctor

Having open discussions with your doctor and cancer team is key to understanding your cancer. Some questions you can ask during your office visit include:

  • What type of lung cancer do I have?
  • Has my cancer spread?
  • Should I have genetic tests for lung cancer?
  • How much does genetic testing cost? Is it covered by insurance?
  • How will I know if my treatment is working?

Patient Resources

American Cancer Society
https://www.cancer.org/cancer/lung-cancer.html
American Lung Association
www.lung.org
Lungcancer.org
www.lungcancer.org/find_information
Free to Breathe
www.freetobreathe.org/

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