Non-small cell lung cancer (NSCLC) accounts for about 80–85% of lung cancer cases in the United States.

This information comes from the American Cancer Society (ACS).

Checkpoint inhibitors are a newer form of therapy that helps the body’s immune system target cancer cells.

Keep reading to learn more about how these drugs prevent cancer cells from growing and spreading to other areas of the body.

Immune checkpoints act as signals to prevent the immune system from attacking healthy cells in the body.

According to the National Cancer Institute (NCI), immune checkpoints activate when the T cells of the immune system bind to a protein on a healthy cell or a cancer cell. When this happens, the immune system ignores the cell. As a result, cancer cells that use a protein to bind with T cells are allowed to continue to grow and spread.

Checkpoint inhibitors prevent cancer cells from binding to T cells. As a result, the immune system can find and target the cancer cells. Some research indicates that the use of checkpoint inhibitors has shown statistically significant improvements in people with NSCLC.

However, these drugs are not without risk. Research states that checkpoint inhibitors can cause immune-related side effects or adverse reactions.

A person should talk with a doctor about the possible benefits and risks before starting checkpoint inhibitor therapy.

The ACS indicates that there are two main types of checkpoint inhibitors used to treat NSCLC. They are PD-1/PD-L1 inhibitors and CTLA-4 inhibitors.

Each type works by targeting a different protein on the T cell. Both types can help the immune system target cancer cells, and they each have potential side effects.

PD-1/PD-L1 inhibitors

According to a recent study, PD-1/PD-L1 inhibitors are a first-line immunotherapy to treat a variety of cancers, including lung cancer.

However, these inhibitors can also cause severe immune-related adverse reactions. More research into novel PD-1/PD-L1 inhibitors that will produce fewer adverse reactions is vital for safety and efficacy.

The ACS indicates that there are five PD-1/PD-L1 inhibitors available for the treatment of NSCLC. They are:

  • nivolumab (Opdivo), PD-1
  • pembrolizumab (Keytruda), PD-1
  • cemiplimab (Libtayo), PD-1
  • atezolizumab (Tecentriq), PD-L1
  • durvalumab (Imfinzi), PD-L1

A doctor may prescribe PD-1/PD-L1 medications as a first-line treatment either with or without other therapies. Some are for more advanced cases of lung cancer. A person will receive these medications intravenously every 2, 3, 4, or 6 weeks.

Research indicates that a doctor should test a person for the presence of PD-L1 expression on cancer cells. People are more likely to respond favorably to the therapy if the cancer cells have these proteins.

CTLA-4 inhibitors

CTLA-4 is another type of protein that a cancer cell may use to evade detection from the immune system.

According to the ACS, there are two CTLA-4 inhibitors for NSCLC. They are called ipilimumab (Yervoy) and tremelimumab (Imjudo). These are drugs that boost the immune response, but block CTLA-4, another protein on T cells that normally helps keep them in check. A person will receive this medication intravenously every 6 weeks.

A doctor may prescribe these drugs along with a PD-1 inhibitor — Yervoy with nivolumab and Imjudo with durvalumab with or without chemotherapy. However, they will not give this medication on its own.

Both types of checkpoint inhibitors can cause side effects to occur.

According to the NCI, several factors can affect the side effects a person will experience.

Factors that affect the severity of side effects include:

  • the person’s health before starting the medication
  • the type of immune checkpoint inhibitor
  • the type of cancer
  • the dose
  • how advanced the cancer is

The most common side effects can include:

  • constipation
  • joint pain
  • cough
  • loss of appetite
  • nausea
  • itching
  • fatigue
  • rash
  • diarrhea

Serious side effects can occur as well. According to the ACS, serious side effects occur more often with CTLA-4 inhibitor therapy than with PD-1/PD-L1 inhibitor therapy.

Serious side effects include autoimmune reactions and infusion reactions.

Autoimmune reactions occur when the immune system attacks healthy cells in other organs, such as the lungs, liver, or kidneys. This can result in life threatening emergencies.

Infusion reactions are similar to allergic reactions. The ACS states that serious side effects are seen more often in CTLA-4 therapy than in PD-1/PD-L1 therapy.

A person should talk with a doctor before starting checkpoint inhibitors, as they can cause serious reactions in some people.

Doctors are not able to determine ahead of time if a person will experience side effects. As a result, a person should contact a doctor if they notice any new symptoms.

If symptoms cause a person to experience difficulty breathing or other severe reactions, they need emergency care immediately.

Checkpoint inhibitors are one first-line treatment for NSCLC. There are two main types: PD-1/PD-L1 inhibitors and CTLA-4 inhibitors. Both can help the immune system target and attack cancer cells.

Both can cause side effects, however, so a person should talk with a doctor about the pros and cons of their use. They should also let the doctor know right away if they notice any side effects or severe reactions.