Immunotherapy for Non-Small Cell Lung Cancer

Immunotherapy is the use of medicines to help a person’s own immune system to recognize and destroy cancer cells more effectively.  

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoint” proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Drugs that target these checkpoints (called checkpoint inhibitors) can be used to treat some people with non-small cell lung cancer (NSCLC).

PD-1/PD-L1 inhibitors

Nivolumab (Opdivo), pembrolizumab (Keytruda), and cemiplimab (Libtayo) target PD-1, a protein on certain immune cells (called T cells) that normally helps keep these cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

Atezolizumab (Tecentriq) and durvalumab (Imfinzi) target PD-L1, a protein related to PD-1 that is found on some tumor cells and immune cells. Blocking this protein can help boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

These drugs can be used in different situations to treat NSCLC. In some cases, before one of these drugs can be used, lab tests might need to be done on the cancer cells to show they have at least a certain amount of the PD-L1 protein (which would mean these drugs are more likely to work).

• Nivolumab can be used along with chemotherapy as a first treatment before surgery (known as neoadjuvant treatment) in some people with early-stage NSCLC.
• Pembrolizumab, atezolizumab, or cemiplimab can be used (sometimes with chemo) as part of the first treatment in some people with metastatic NSCLC.
• Nivolumab can be an option as part of the first treatment in some people with metastatic NSCLC, along with CTLA-4 inhibitor ipilimumab (Yervoy), which is described below. Similarly, durvalumab can be given along with the CTLA-4 inhibitor tremelimumab (Imjudo). Chemo is often given along with these treatments as well.
• Nivolumab, pembrolizumab, and atezolizumab can also be used in people with certain types of advanced NSCLC whose cancer starts growing again after chemotherapy or other drug treatments.
• For people with stage III NSCLC who cannot have surgery or chemotherapy with radiation, pembrolizumab or cemiplimab can be given as the first treatment.
• Durvalumab can be used in people with stage III NSCLC whose cancer cannot be removed with surgery and has not gotten worse after they have received chemotherapy with radiation (chemoradiation). The goal of treatment with this drug (also called consolidation therapy) is to keep the cancer from getting worse for as long as possible.
• Atezolizumab or pembrolizumab can be used in people with some earlier stages of NSCLC who have already been treated with surgery followed by chemotherapy. This known as adjuvant therapy.

All of these drugs are given as an intravenous (IV) infusion. Depending on the drug, they might be given every 2, 3, 4, or 6 weeks.

Possible side effects

Side effects of these drugs can include fatigue, cough, nausea, itching, skin rash, loss of appetite, constipation, joint pain, and diarrhea.

Other, more serious side effects occur less often.

Infusion reactions: Some people might have an infusion reaction while getting these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting these drugs.

Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

It’s very important to report any new side effects to your health care team as soon as possible. If serious side effects do occur, treatment may need to be stopped and you may get high doses of corticosteroids to suppress your immune system.

CTLA-4 inhibitors

Ipilimumab (Yervoy) and tremelimumab (Imjudo) are also drugs that boost the immune response, but they block CTLA-4, another protein on T cells that normally helps keep them in check.

These drugs are used along with a PD-1 inhibitor (ipilimumab with nivolumab, and tremelimumab with durvalumab); they are not used alone. They might be an option as part of the first treatment for certain types of advanced NSCLC, most often along with chemo as well.

These drugs are given by intravenous (IV) infusion, usually once every 3 or 6 weeks. 

Possible side effects

The most common side effects of these drugs include fatigue, diarrhea, skin rash, itching, muscle or bone pain, and belly pain.

Serious side effects seem to happen more often with CTLA-4 inhibitors than with the PD-1 and PD-L1 inhibitors. 

Autoimmune reactions: These drugs can sometimes cause the immune system to attack other parts of the body, which can lead to serious problems in the intestines, liver, hormone-making glands, nerves, skin, eyes, or other organs. In some people these side effects can be life threatening.

Infusion reactions: Some people might have an infusion reaction while getting one of these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting an infusion.

It’s very important to report any new side effects during or after treatment with any of these drugs to your health care team promptly. If serious side effects do occur, you may need to stop treatment and take high doses of corticosteroids to suppress your immune system.