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) and pembrolizumab (Keytruda) 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) targets 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.

  • Pembrolizumab or atezolizumab can be used with or without chemo as part of the first treatment in some people with advanced NSCLC. Nivolumab can also be an option as the first treatment in some people. It is given along with CTLA-4 inhibitor ipilimumab (Yervoy), which is described below, sometimes along with chemo 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 can be given as the first treatment.

Durvalumab (Imfinzi) also targets the PD-L1 protein, but this drug is used a little differently than the other PD-1/PD-L1 inhibitors. It is 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.

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 inhibitor

Ipilimumab (Yervoy) is another drug that boosts the immune response, but it has a different target. It blocks CTLA-4, another protein on T cells that normally helps keep them in check.

This drug can be used along with the PD-1 inhibitor nivolumab (Opdivo), with or without chemo, to treat certain types of advanced NSCLC, but it’s not used alone.

This drug is given as an intravenous (IV) infusion, usually once every 6 weeks. 

Possible side effects

The most common side effects from this drug include fatigue, diarrhea, skin rash, and itching.

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

  • Like those drugs, this drug can 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.
  • Some people might have an infusion reaction while getting this drug. 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 this drug.

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.

More information about immunotherapy

To learn more about how drugs that work on the immune system are used to treat cancer, see Cancer Immunotherapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.

Araujo LH, Horn L, Merritt RE, Shilo K, Xu-Welliver M, Carbone DP. Ch. 69 - Cancer of the Lung: Non-small cell lung cancer and small cell lung cancer. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Chiang A, Detterbeck FC, Stewart T, Decker RH, Tanoue L. Chapter 48: Non-small cell lung cancer. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2019.

National Cancer Institute. Physician Data Query (PDQ). Health Professional Version. Non-Small Cell Lung Cancer Treatment. 2019. Accessed at https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq on June 10, 2019.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. V.4.2019. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf on June 10, 2019.

Paik PK, Pillai RN, Lathan CS, Velasco SA and Papadimitrakopoulou V. New Treatment Options in Advanced Squamous Cell Lung Cancer. Am Soc Clin Oncol Educ Book. 2019;39:e198-e206.

Reck M and Rabe KF. Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):849-861.

References

Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.

Araujo LH, Horn L, Merritt RE, Shilo K, Xu-Welliver M, Carbone DP. Ch. 69 - Cancer of the Lung: Non-small cell lung cancer and small cell lung cancer. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Chiang A, Detterbeck FC, Stewart T, Decker RH, Tanoue L. Chapter 48: Non-small cell lung cancer. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2019.

National Cancer Institute. Physician Data Query (PDQ). Health Professional Version. Non-Small Cell Lung Cancer Treatment. 2019. Accessed at https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq on June 10, 2019.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. V.4.2019. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf on June 10, 2019.

Paik PK, Pillai RN, Lathan CS, Velasco SA and Papadimitrakopoulou V. New Treatment Options in Advanced Squamous Cell Lung Cancer. Am Soc Clin Oncol Educ Book. 2019;39:e198-e206.

Reck M and Rabe KF. Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):849-861.

Last Revised: May 27, 2020

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.