If your non-small cell lung cancer (NSCLC) involves a gene mutation, you may receive a targeted therapy. These medications address specific gene mutations more effectively than standard cancer treatments.

Cancer can be caused by mutations, which are changes in the genes that control cell growth and division. These mutations enable cells to grow out of control and form tumors.

In the 1980s, researchers discovered the first of many gene mutations for lung cancer. This discovery eventually led to the introduction of targeted drug therapies, which address specific gene mutations.

Before targeted therapies, everyone with non-small cell lung cancer (NSCLC) followed a similar regimen. That might have included surgery, radiation, chemotherapy, or a combination of these treatments.

Targeted therapies work by blocking the signals that help certain NSCLCs grow and spread. They can help improve some people’s survival.

If you have received an NSCLC diagnosis, your doctor can let you know whether you should be tested for gene mutations. Tests can help your doctor find the most effective treatment for your cancer and predict how well your cancer might respond.

To find the most effective treatment, your doctor has to first gather some information about your cancer and its specific mutations.

The tumor type

Different types of tumors respond differently to treatments.

The three main subtypes of NSCLC include:

  • Adenocarcinomas: These start in mucus-producing cells of the lungs.
  • Large cell carcinomas: These can start in any part of the lung. They often grow quickly.
  • Squamous cell carcinomas: These start in cells lining the lung’s airways.

The stage of cancer and how aggressive it is

Early stage NSCLCs have not grown beyond the lung. Surgery may be an option for people with these tumors.

Some cancers spread faster than others and require different kinds of treatment.

Once cancer has spread outside the lung, treatments may include:

The tumor’s specific gene mutations

Mutated genes produce proteins that help cancer cells grow. Targeted therapies block these proteins, which prevents the cancer cells from spreading.

Your doctor must understand which gene mutations are in your tumor to determine the right targeted therapy.

The KRAS and epidermal growth factor receptor (EGFR) mutations are among the most common gene mutations doctors test for in NSCLC.

A doctor or pathologist can use various techniques to test for mutations.

Analyzing a sample of tissue from your lung, and sometimes the lymph nodes around your lungs, can provide a healthcare professional with the information they need to guide your treatment. They’ll remove this tissue with a needle during a biopsy.

They may also take a blood sample instead, which is known as a liquid biopsy.

They may personally analyze the tissue sample or send it to a lab for genetic testing.

Genetic testing techniques include:

  • Fluorescence in situ hybridization (FISH): This highly accurate technique uses special dyes to visualize and map your genes or chromosomes.
  • Immunohistochemistry: Immunohistochemistry is a widely available staining technique.
  • Next-generation sequencing (NGS): During next-generation sequencing (NGS), a healthcare professional runs your tissue or blood sample through a machine.

Your cancer will be screened for gene mutations and other biomarkers. Knowing which biomarkers you have can help the healthcare professional personalize your treatment.

If your test results come back positive for a gene mutation, your doctor can give you medications that specifically target the mutation. Keep in mind that it’s possible to have more than one gene mutation at the same time.

Because targeted therapies focus on addressing the specific abnormalities that help tumors survive, they’re more effective than traditional cancer treatments such as chemotherapy and radiation. Targeted therapies may also have fewer side effects.

Targeted therapies may be taken on their own, combined with one another, or combined with other lung cancer treatments.

KRAS

The KRAS mutation is one of the most common gene mutations in NSCLC, found in about 30% of cases.

If you have this mutation, you may receive the targeted therapy sotorasib (Lumakras) or adagrasib (Krazati).

Adagrasib is intended for people who’ve already tried a systemic therapy such as chemotherapy.

EGFR

Epidermal growth factor receptors (EGFRs) are proteins on the surface of some cancer cells. They help the cells grow and divide. A mutation in the EGFR gene turns on these receptors, which allows cancer cells to grow faster.

The EGFR mutation is involved in around 10% to 15% of lung cancers in the United States.

There are various subtypes of the EGFR mutation. Your treatment options depend on your subtype. Some subtypes don’t respond to targeted therapies.

EGFR inhibitors block the signals that EGFR-positive cancers need to grow. This group of drugs includes:

  • afatinib (Gilotrif)
  • dacomitinib (Vizimpro)
  • erlotinib (Tarceva)
  • gefitinib (Iressa)
  • osimertinib (Tagrisso)
  • necitumumab (Portrazza), which must be combined with the chemotherapy drugs gemcitabine (Infugem) and cisplatin
  • lazertinib (Lazcluze), which must be combined with amivantamab (Rybrevant)
  • erlotinib, which must be combined with a VEGF inhibitor (ramucirumab or bevacizumab)

The following antibody treatment is also available:

  • amivantamab-vmjw (Rybrevant), which may be combined with chemotherapy

Amivantamab-vmjw (Rybrevant) may be given to people who’ve already tried chemotherapy.

Anaplastic lymphoma kinase (ALK)

About 4 to 6% of NSCLCs have a change in the anaplastic lymphoma kinase (ALK) gene.

If you have an ALK or EML4-ALK mutation, your cancer may respond to one of these drugs:

  • alectinib (Alecensa)
  • brigatinib (Alunbrig)
  • ceritinib (Zykadia)
  • crizotinib (Xalkori)
  • lorlatinib (Lorbrena)
  • ensartinib (Ensacove)

Mesenchymal-epithelial transition (MET) and METex14

The mesenchymal-epithelial transition (MET) gene is involved in signaling pathways that control cell growth, survival, and spread.

Up to 5% of NSCLCs involve the MET mutation. The METex14 mutation is a subtype linked to around 3% of NSCLCs.

Targeted therapies that help treat cancers caused by the METex14 mutation include:

  • capmatinib (Tabrecta)
  • tepotinib (Tepmetko)
  • crizotinib (Xalkori)

At the moment, there are no FDA-approved treatments for other subtypes.

BRAF and BRAF V600E

Up to 3.5% to 4% of NSCLCs involve the BRAF mutation.

Two targeted therapies are available to help treat cancers caused by the BRAF V600E subtype:

  • dabrafenib (Tafinlar) with trametinib (Mekinist)
  • encorafenib (Braftovi) with binimetinib (Mektovi)

If a person cannot take combination therapy, they may be able to take the following drugs as stand-alone treatments:

  • vemurafenib (Zelboraf)
  • dabrafenib (Tafinlar)

There are no FDA-approved treatments for other subtypes.

Human epidermal growth factor receptor 2 (HER2)

The human epidermal growth factor receptor 2 (HER2) gene mutation is involved in 1% to 4% of NSCLCs.

Targeted therapies to help treat HER-2 positive NSCLC include:

  • fam-trastuzumab deruxtecan-nxki (Enhertu)
  • ado-trastuzumab emtansine (Kadcyla)
  • zenocutuzumab-zbco (Bizengri)

Neurotrophic tyrosine receptor kinase (NTRK)

The neurotrophic tyrosine receptor kinase (NTRK) mutation causes around 1% of NSCLCs.

Two targeted therapies are available to help treat these cancers:

  • entrectinib (Rozlytrek)
  • larotrectinib (Vitrakvi)

RET

The RET mutation is found in 1% to 2% of NSCLCs.

There are two RET inhibitors:

  • pralsetinib (Gavreto)
  • selpercatinib (Retevmo)

Cabozantinib (Cometriq, Cabometyx), a multi-kinase inhibitor, also targets RET.

ROS1

About 1% to 2% of NSCLCs have the ROS1 mutation.

The ROS1 mutation is similar to the ALK mutation. Some of the same drugs help treat both mutations.

Targeted therapies for ROS1-positive lung cancer include:

  • ceritinib (Zykadia), which also helps treat ALK-positive lung cancer
  • crizotinib (Xalkori), which also helps treat ALK-positive lung cancer
  • entrectinib (Rozlytrek), which also helps treat NTRK-positive lung cancer
  • repotrectinib (Augtyro), which also helps treat NTRK-positive lung cancer
  • lorlatinib (Lorbrena), which also helps treat ALK-positive lung cancer

The FDA has not approved ceritinib (Zykadia) and lorlatinib (Lorbrena) for treating ROS1-positive lung cancers. These drugs are considered off-label drugs when used to treat these cancers.

OFF-LABEL DRUG USE

Off-label drug use means a drug that’s approved by the Food and Drug Administration (FDA) for one purpose is used for a different purpose that hasn’t yet been approved.

However, a doctor can still use the drug for that purpose. This is because the FDA regulates the testing and approval of drugs but not how doctors use drugs to treat their patients.

So your doctor can prescribe a drug however they think is best for your care.

Your doctor typically lets you know whether your cancer should be tested for gene mutations. The results of a genetic test can help your doctor find a targeted therapy that’s more likely to work against your specific type of cancer.

Targeted therapies usually have fewer side effects than chemotherapy or other standard treatments.

There are no FDA-approved targeted therapies yet for cancer involving these specific mutations:

  • NRAS
  • PIK3CA
  • TP53, which is the most common lung cancer mutation overall

If a treatment isn’t available for your specific mutation, you may be able to join a clinical trial of a new drug that’s under investigation.