Non-small cell lung cancer (NSCLC) is a term for a condition caused by more than one genetic mutation in the lungs. Testing for these different mutations can affect treatment decisions and outcomes.

Continue reading to learn about the different types of NSCLC, and the tests and treatments available.

What are genetic mutations?

Genetic mutations, whether inherited or acquired, play a role in the development of cancer. Many mutations involved in NSCLC have already been identified. This has helped researchers develop drugs that target some of those specific mutations.

Knowing which mutations are driving your cancer can give your doctor an idea of how the cancer will behave. This can help determine which drugs are most likely to be effective. It can also identify powerful drugs that are unlikely to help in your treatment.

This is why genetic testing after a diagnosis of NSCLC is so important. It helps to personalize your treatment.

The number of targeted treatments for NSCLC continues to grow. We can expect to see more advances as researchers discover more about specific genetic mutations that cause NSCLC to progress.

How many types of NSCLC are there?

There are two main types of lung cancer: small cell lung cancer and non-small cell lung cancer. About 80 to 85 percent of all lung cancers are NSCLC, which can be further divided into these subtypes:

  • Adenocarcinoma starts in young cells that secrete mucus. This subtype is usually found in outer parts of the lung. It tends to occur more often in women than in men and in younger people. It’s generally a slow-growing cancer, making it more discoverable in early stages.
  • Squamous cell carcinomas start in the flat cells that line the inside of the airways in your lungs. This type is likely to start near the main airway in the middle of the lungs.
  • Large cell carcinomas can start anywhere in the lung and can be quite aggressive.

Less common subtypes include adenosquamous carcinoma and sarcomatoid carcinoma.

Once you know which type of NSCLC you have, the next step is usually to determine the specific genetic mutations that might be involved.

What do I need to know about genetic tests?

When you had your initial biopsy, your pathologist was checking for the presence of cancer. The same tissue sample from your biopsy can usually be used for genetic testing. Genetic tests can screen for hundreds of mutations.

These are some of the most common mutations in NSCLC:

  • EGFR mutations occur in about 10 percent of people with NSCLC. Approximately half of people with NSCLC who’ve never smoked are found to have this genetic mutation.
  • EGFR T790M is a variation in the EGFR protein.
  • KRAS mutations are involved about 25 percent of the time.
  • ALK/EML4-ALK mutation is found in about 5 percent of people with NSCLC. It tends to involve younger people and nonsmokers, or light smokers with adenocarcinoma.

Less common genetic mutations associated with NSCLC include:

  • BRAF
  • HER2 (ERBB2)
  • MEK
  • MET
  • RET
  • ROS1

How do these mutations affect treatment?

There are many different treatments for NSCLC. Because not all NSCLC is the same, treatment must be carefully considered.

Detailed molecular testing can tell you if your tumor has particular genetic mutations or proteins. Targeted therapies are designed to treat the specific characteristics of the tumor.

These are some targeted therapies for NSCLC:

EGFR

EGFR inhibitors block the signal from the EGFR gene that encourages growth. These include:

  • afatinib (Gilotrif)
  • erlotinib (Tarceva)
  • gefitinib (Iressa)

These are all oral medications. For advanced NSCLC, these drugs can be used alone or with chemotherapy. When chemotherapy isn’t working, these drugs can still be used even if you don’t have the EGFR mutation.

Necitumumab (Portrazza) is another EGFR inhibitor used for advanced squamous cell NSCLC. It’s given via intravenous (IV) infusion in combination with chemotherapy.

EGFR T790M

EGFR inhibitors shrink tumors, but these drugs can eventually stop working. When that happens, your doctor may order an additional tumor biopsy to see if the EGFR gene has developed another mutation called T790M.

In 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to osimertinib (Tagrisso). This drug treats advanced NSCLC involving the T790M mutation. The drug was granted accelerated approval in 2015. The treatment is indicated when EGFR inhibitors aren’t working.

Osimertinib is an oral medication taken once a day.

ALK/EML4-ALK

Therapies that target abnormal ALK protein include:

  • alectinib (Alecensa)
  • brigatinib (Alunbrig)
  • ceritinib (Zykadia)
  • crizotinib (Xalkori)

These oral medications can be used in place of chemotherapy or after chemotherapy has stopped working.

Other treatments

Other targeted therapies include:

  • BRAF: dabrafenib (Tafinlar)
  • MEK: trametinib (Mekinist)
  • ROS1: crizotinib (Xalkori)

Currently, there is no approved targeted therapy for the KRAS mutation, but research is ongoing.

Tumors need to form new blood vessels to continue to grow. Your doctor may prescribe therapy to block new blood vessel growth in advanced NSCLC, such as:

  • bevacizumab (Avastin), which may be used with or without chemotherapy
  • ramucirumab (Cyramza), which can be combined with chemotherapy and is usually given after other treatment is no longer working

Other treatments for NSCLC may include:

  • surgery
  • chemotherapy
  • radiation
  • palliative therapy to ease symptoms

Clinical trials are a way to test the safety and effectiveness of experimental therapies that aren’t yet approved for use. Talk to your doctor if you’d like to learn more about clinical trials for NSCLC.