Immunotherapy for Lung Cancer

January 24, 2025

This page was reviewed under our medical and editorial policy by Jyoti Malhotra, M.D., M.P.H., associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope^® Orange County Lennar Foundation Cancer Center; and Jae Y. Kim, M.D., associate professor, Division of Thoracic Surgery, Department of Surgery, City of Hope Cancer Center Duarte

Immunotherapy may be an option for treating certain types of lung cancer. It works by using the body’s immune system to fight cancer, either by boosting its natural ability to target cancer cells or by introducing lab-made substances that help the immune system work more successfully.

The U.S. Food and Drug Administration (FDA) first approved immunotherapy for lung cancer in 2015 with the drug Opdivo^® (nivolumab) for advanced non-small cell lung cancer (NSCLC). Since then, more immunotherapy drugs have been approved. It is even being used as a primary treatment for some patients with lung cancer.

What Is Immunotherapy for Lung Cancer?

Immunotherapy helps the body’s immune system fight cancer. The immune system is a network of organs, cells and substances that work together to protect the body from diseases. While it is good at identifying germs or harmful invaders, it has a harder time spotting cancer cells. This is because cancer starts in normal, healthy cells that change and begin growing uncontrollably. Since these cancer cells were once normal, the immune system does not always recognize them as a threat.

Immunotherapy helps the immune system find and attack cancer cells. It strengthens the body’s natural defenses or uses lab-created substances that mimic immune system components. Several different subtypes of immunotherapy may be used for cancer treatment.

Checkpoint inhibitors: These drugs help improve the immune system’s ability to find and destroy cancer cells. 

Monoclonal antibodies: These lab-created immune system proteins are designed to attack specific parts of cancer cells.

Immunotherapy differs from traditional lung cancer treatments like chemotherapy, radiation therapy and surgery. Chemotherapy for lung cancer uses drugs that travel through the whole body to destroy cancer cells directly, while surgery and radiation therapy target specific areas of the body. These types of cancer treatments do not rely on the immune system for their effects.

Immune Checkpoint Inhibitors

One common type of immunotherapy medicine used to treat lung cancer is immune checkpoint inhibitors. These drugs help the immune system recognize and attack cancer cells.

Normally, the immune system uses proteins called “checkpoints” to tell the difference between healthy cells and harmful ones like cancer cells. Cancer may sometimes trick these checkpoints and avoid being attacked. Checkpoint inhibitors block the cancer’s ability to hide, allowing the immune system to do its job.

These drugs do not directly destroy cancer cells but instead make it easier for the body’s natural defenses to find and destroy them. This action might help treat various types of cancer, including lung cancer.

PD-1/PD-L1 Inhibitors

PD-1/PD-L1 inhibitors are a type of immune checkpoint inhibitor used to treat both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). PD-1 is a checkpoint protein found on immune cells called T cells.

Commonly, PD-1 acts as an off switch when it binds to PD-L1, a protein found on some healthy and cancer cells. This binding tells the immune system to leave those cells alone, allowing some cancer cells to hide from being attacked.

PD-1/PD-L1 inhibitors block this binding and increase the immune system’s ability to find and destroy cancer cells. These inhibitors are given through an intravenous (IV) infusion, typically every two to six weeks, depending on the specific drug.

For NSCLC, drugs like Opdivo^® (nivolumab), Keytruda^® (pembrolizumab) and Libtayo^® (cemiplimab) target PD-1, while Tecentriq^® (atezolizumab) and Imfinzi® (durvalumab) target PD-L1. Providers may use these drugs in combination with other treatments, such as chemotherapy. They are often used for advanced-stage cancers.

In the case of SCLC, Tecentriq^® (atezolizumab) and Imfinzi® (durvalumab) are commonly used as part of the first line of treatment, along with chemotherapy. After the initial chemotherapy, these drugs may be continued as maintenance therapy to keep the cancer from growing.

Some forms of Tecentriq^® (atezolizumab) may also be given as an injection under the skin, typically once every three weeks, making the treatment more convenient for patients.

CTLA-4 Inhibitors

CTLA-4 inhibitors are another type of immune checkpoint inhibitor used to treat advanced NSCLC. CTLA-4 is a checkpoint protein found on T cells. Normally, CTLA-4 acts as an off switch to prevent T cells from attacking healthy cells. However, cancer sometimes uses this mechanism to avoid the immune system’s attack.

Drugs like Yervoy^® (ipilimumab) and Imjudo^® (tremelimumab) block CTLA-4, allowing the immune system to become more active in targeting cancer cells. These drugs are not used alone but are typically combined with PD-1 inhibitors, such as Opdivo® (nivolumab) or Imfinzi^® (durvalumab), to boost the overall immune response.

Depending on the specific treatment plan, CTLA-4 inhibitors are usually given as IV infusions every three to six weeks. They may be used as part of the first line of treatment for advanced NSCLC and may be combined with chemotherapy.

Risks and Side Effects

Immunotherapy for lung cancer may cause side effects, but not everyone experiences the same ones. These side effects vary depending on the specific drugs used, the length of treatment and whether immunotherapy is combined with other treatments like chemotherapy. It is important to report any side effects to the care team immediately.

Some common side effects of lung cancer immunotherapy with immune checkpoint inhibitors may include the following.

Constipation: Trouble passing stool.

Fatigue: Feeling extremely tired, even after rest.

Joint pain: Aching or discomfort in the joints.

Cough: A persistent cough that starts after treatment.

Diarrhea: Loose or watery stools.

Nausea: Feeling sick to the stomach, which may lead to vomiting.

Skin rash: Red, itchy or irritated patches of skin.

Loss of appetite: Not feeling hungry or losing interest in food.

Muscle or bone pain: Discomfort or soreness in muscles or bones.

Belly pain: Pain or discomfort in the abdomen.

Itching: Persistent itchiness, with or without a rash.

More serious but less common side effects are possible, such as the following.

Infusion reactions: Some people may experience an allergic-like reaction during the IV infusion. This might include symptoms like chills, fever, rash, flushing, dizziness or trouble breathing.

Autoimmune reactions: In some cases, the immune system may mistakenly attack healthy organs like the lungs, liver, intestines or hormone glands. This could be life-threatening if not treated quickly.

Patients are more likely to report serious side effects with CTLA-4 inhibitors than with the PD-1 and PD-L1 inhibitors.

How Long Does Immunotherapy Work for Lung Cancer?

The length of time someone stays on immunotherapy for lung cancer varies. A typical course of treatment lasts up to two years.

In some cases, patients may continue treatment beyond the two-year mark. However, a 2023 study in JAMA Oncology suggests that stopping immunotherapy at two years might be just as successful as continuing longer, especially for those whose cancer has not progressed.

For patients with advanced NSCLC who remain progression-free, it is reasonable to consider stopping immunotherapy after two years. Some concerns with continuing therapy indefinitely include the risk of side effects and the financial burden of ongoing treatment. So far, studies have not shown a clear benefit to staying on immunotherapy longer than two years, but more research is needed.

Doctors may recommend either continuing or stopping treatment based on how the cancer responds and the individual’s overall health. Each person’s situation is different. Patients should decide whether to continue immunotherapy after careful discussion with their care team.