How does it work? Targeted therapy for lung cancer

Cancerous tumors need a steady blood supply to grow. Angiogenesis inhibitors are a type of long-term medication that targets the blood vessels supporting cancer cells. By blocking the growth of these blood vessels, this targeted treatment can slow or stop the growth of lung cancer.

A doctor is most likely to prescribe bevacizumab (Avastin) or ramucirumab (Cyramza) to treat lung cancer.

Side effects vary based on which part of the blood cells the medication targets. Some common side effects can include:

• fatigue
• high blood pressure
• diarrhea
• pain, swelling, tingling, numbness, or flushing in the hands or feet
• hair changes
• protein in the urine
• an increased risk of infections (due to low white blood cell counts)
• biochemical hypothyroidism

Serious side effects are rarer. These may include:

• holes (perforations) and fistulas in the gastrointestinal tract
• severe bleeding (hemorrhage)
• slow would healing
• heart failure
• stroke or heart attack (due to a blockage in the arteries)
• reversible posterior leukoencephalopathy syndrome (a brain condition)

Epidermal growth factor receptor (EGFR) is a protein on the outside of cells that controls their growth and division. EGFR genetic mutations can cause too much EGFR to be present in cells, which causes cancer to grow faster.

The overall prevalence of EGFR mutations is about 32.3% and is higher in females than males (43.7% vs. 24.0%). It is also more than double in people who smoke (49.3% vs. 21.5%).

“For advanced-stage NSCLC with common EGFR mutations, EGFR targeted therapy such as osimertinib is the preferred first line of treatment,” said Dr. Byun.

EGFR inhibitors block the signals from EGFR to prevent the growth and division of cancer cells.

Some common EGFR inhibitors for lung cancer include:

• afatinib (Gilotrif)
• osimertinib (Tagrisso)
• erlotinib (Tarceva)
• dacomitinib (Vizimpro)
• gefitinib (Iressa)

Some common side effects of EGFR inhibitors can include:

• appetite suppression
• diarrhea
• skin problems, which can lead to skin infections
• mouth sores

These side effects can be severe enough that doctors recommend that people stop taking EGFR inhibitors.

“For example,” said Dr. Byun, “if a patient experiences a severe adverse reaction such as interstitial lung disease related to osimertinib, which occurs infrequently, then the medication is discontinued and the patient would be considered for chemotherapy.”

EGFR inhibitors that target cells with the T790M mutation

According to one 2018 study, most people with lung cancer develop resistance to EGFR inhibitors. This is often because the cancer cells develop new EGFR mutations. One common mutation is called T790M.

Osimertinib (Tagrisso) is a drug that targets cells with the T790M mutation. The side effects of this drug are similar to those of other EGFR inhibitors.

EGFR inhibitors used for squamous cell NSCLC

Necitumumab (Portrazza) is an EGFR inhibitor that mimics immune system proteins.

A doctor will give the medication intravenously and will often prescribe it with chemotherapy for people with advanced squamous cell NSCLC. It can cause similar side effects to those of other EGFR inhibitors.

EGFR inhibitors used for Exon 20 mutation

There is a rarer EGFR mutation known as Exon 20 which does not respond to many medications. However, researchers have developed some targeted drugs to target cancer resulting from this mutation as well.

These are medications are amivantamab (Rybrevant) and mobocertinib (Exkivity). Doctors will typically prescribe these medications after unsuccessful chemotherapy. The side effects are similar to those of other EGFR inhibitors.

Anaplastic lymphoma kinase (ALK) is a protein that supports cell growth. Some people with lung cancer have a mutation in the ALK gene, which causes more ALK proteins to form. This drives cancer growth and spread.

According to research, smoking may not be a major fact in the development of lung cancer related to an ALK mutation. ALK mutations are more common in non-smokers than smokers.

ALK inhibitors are medications that target cancers with the ALK mutation. Certain people can use them after or instead of chemotherapy.

Some examples of these drugs include:

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

It is possible to experience side effects from taking this drug, including:

• vision changes
• fatigue
• constipation
• nausea and vomiting
• diarrhea

Some more severe and rare side effects include:

• heart rhythm problems
• liver or nerve damage
• swelling in the lungs or throughout the body

The American Cancer Society estimates that 1–2% of NSCLC cases have a ROS1 mutation, which affects how cancer cells grow and spread.

According to one recent study, ROS1 inhibitors are a well-established targeted therapy for people with a type of NSCLC lung cancer known as adenocarcinoma. Adenocarcinoma accounts for 50–60% of lung cancer in people who don’t smoke.

If a doctor identifies a ROS1 mutation, they may prescribe one of the following medications:

• lorlatinib (Lorbrena)
• crizotinib (Xalkori)
• ceritinib (Zykadia)
• entrectinib (Rozlytrek)

People can use these medications instead of chemotherapy or when chemotherapy or other therapies stop working. Some potential side effects may include:

• constipation
• dizziness
• diarrhea
• vision problems
• fatigue

More severe side effects may include:

• liver or nerve damage
• swelling in the lungs or elsewhere in the body
• heart problems

About 1–2% of people with NSCLC develop RET gene mutations. These changes affect a protein involved in cell growth, and they often occur with other mutations. As a result, a doctor may prescribe RET-targeting medications with EGFR-targeting medications for the best effect against cancer.

Medications to target RET genes include selpercatinib (Retevmo) and pralsetinib (Gavreto).

Some common side effects can include:

• rash
• high blood pressure
• dry mouth
• diarrhea or constipation
• joint pain
• hand and feet swelling
• elevated blood sugar levels
• muscle pain
• feeling tired
• changes in some blood test results
• low blood counts

More severe and rare side effects may include:

• problems with wound healing
• bleeding
• lung or liver damage
• heart rhythm changes
• allergic reactions

According to one 2015 study, changes in the mesenchymal-epithelial transition (MET) gene are present in about 5% of lung cancer cases. The MET gene creates the MET protein, which is involved in cell invasion, growth, migration, and metastasis.

Capmatinib (Tabrecta) is the first FDA-approved MET-targeting medication for treating metastatic NSCLC. Another recently approved drug is tepotinib (Tepmetko).

Researchers are currently studying many other types of MET-inhibitor, including emibetuzumab, tivantinib, cabozantiniband, and onartuzumab.

Some potential side effects of these drugs may include:

• lack of appetite
• swelling in the hands or feet
• constipation
• nausea
• vomiting
• weakness or tiredness
• diarrhea
• changes in some blood test results
• sun sensitivity

Rarely, these drugs can cause liver damage and swelling or scarring in the lungs.

Recent research suggests that very few people with NSCLC develop an NTRK gene change that can cause the cancer to grow and spread.

Doctors typically prescribe two medications for this mutation in people with advanced lung cancer: larotrectinib (Vitrakvi) and entrectinib (Rozlytrek). Both are typically given when the cancer does not respond to other treatments.

Some potential side effects include:

• diarrhea
• dizziness
• fatigue
• constipation
• vomiting
• weight gain
• nausea

Some other, less common side effects include:

• confusion
• heart problems
• irregular liver test results

According to research, about 4% of people with NSCLS have a BRAF mutation. This causes a change to BRAF proteins, which causes cells with these proteins to grow.

The two targeted medications doctors commonly use to treat lung cancer with a BRAF mutation are dabrafenib (Tafinlar) and trametinib (Mekinist). Dabrafenib attacks BRAF proteins directly. Trametinib attacks related MEK proteins. Doctors may use these medications together to treat metastatic NSCLC in some cases.

Some potential side effects include:

• skin thickening, rash, or itching
• sensitivity to the sun
• headache
• fever
• joint pain
• fatigue
• hair loss
• nausea
• diarrhea

Rarer side effects include:

• bleeding
• heart rhythm problems
• liver or kidney problems
• other lung problems
• serious llergic reaction
• severe skin or eye problems
• high blood sugar

Approximately 1 in 4 people with NSCLC have a KRAS mutation. Among these, 13% will have a specific mutation known as KRAS G12C.

People with this mutation are resistant to many other targeted medications. Doctors commonly use Sotorasib (Lumakras) to treat cancer with this type of mutation. The medication works by attaching to the KRAS G12C protein and preventing the cancer cell from growing.

The side effects can include:

• diarrhea
• joint or muscle pain
• nausea
• fatigue or weakness
• cough
• Low white or red blood cell counts

Rarer serious side effects can include:

• liver damage
• swelling or swelling in the lungs
• difficulty breathing

A number of different drugs provide targeted treatment for many people with lung cancer.

These medications work by honing in on certain mutations in genes involved in lung cancer and stopping the reproduction, growth, and spread of cancer cells.

People may use targeted therapies with, instead of, or following other cancer therapies, including chemotherapy.

What is the most effective treatment for non-small cell lung cancer?

There is no one most effective treatment for any person. This depends on the stage of the disease and how it is progressing. In stages 0-1, surgery may be the only treatment. In stage 2, a person may need surgery followed by chemotherapy. When there are gene mutations present, doctors will also use targeted therapy. In stage 3 and beyond, doctors may prescribe radiation or radiation along with the other treatments. The further the disease develops, the harder it is to cure.

Learn more about treatment for NSCLC.

How long can you live with non-small cell lung cancer?

Overall, about 26% of people with NSCLC survive at least 5 years post-diagnosis. However, this depends on the stage of diagnosis. The more cancer has spread at diagnosis, the lower the survival period. For example, 64% of people with localized cancer only will survive for 5 years.