Immunotherapies for Non-Small Cell Lung Cancer

Exciting treatments for those with advanced lung cancer

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Immunotherapy modifies some aspects of the body's immune system to help manage a number of illnesses, including non-small cell lung cancer (NSCLC). Certain cancers have distinct molecular features. By identifying them with genetic testing, healthcare providers can select an immunotherapy drug that is designed to attack a patient's specific type of NSCLC in a more targeted way.

Because of the way immunotherapies zero in on cancer cells, they often result in fewer and milder side effects than chemotherapy. Some examples of immunotherapy drugs used for NSCLC include Opdivo, Keytruda, and Tecentriq.

Antibodies attacking a cancer cell
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How Immunotherapy Works in NSCLC

NSCLC is the most common type of lung cancer. It can grow within the lungs and may metastasize (spread) to other regions of the body.

There are a variety of treatments for NSCLC, and immunotherapy might be part of your regimen. Immunotherapy in NSCLC works by modifying the action of immune system checkpoints. This treatment isn't considered suitable as the sole treatment for NSCLC. Rather, it is used in combination with chemotherapy, radiation therapy, and/or surgery. It is also only used when certain conditions, such as disease type and stage and a trial of prerequisite medications, have been met.

What are called immune system checkpoints are natural proteins of the immune system that prevent the destruction of healthy, normal cells. Cancer cells may differ from a person's healthy cells in ways that trigger the T-cells of the immune system to recognize and destroy them before they can cause problems.

But when cancer cells bind to and inactivate immune system checkpoint proteins, the body's immune system may ignore them, allowing the cancer to grow and spread.

Immune checkpoint inhibitors are a category of immunotherapy drugs. They block certain immune system checkpoints so the body will recognize the cancer cells as abnormal and launch an attack on them. There are a variety of immune checkpoint inhibitors, some of which are used for treating NSCLC.

Monoclonal Antibodies

The immunotherapies used to treat NSCLC are monoclonal antibodies. These products are created in a laboratory setting and are designed to bind to certain receptors in the body.

In the case of NSCLC, most monoclonal antibodies are produced to bind to the programmed cell death protein (PD-1) receptors on T-cells or the programmed death ligand 1 (PD-L1 ) proteins on cancer cells, although some interact with other receptors.

PD-L1 and its partner, programmed death ligand 2 (PD-L2), are transmembrane proteins expressed in normal tissues to inhibit the activity of T-cells and prevent autoimmunity. They are considered a major immune system checkpoint involved in NSCLC.

When a lung tumor produces PD-L1 or PD-L2 proteins, these proteins can bind to the PD-1 receptor on T-cells and prevent the immune system from fighting against the cancer cells. This allows the cancer cells to survive and multiply, resulting in cancer progression.

Drugs that block PD-L1, which are called PD-L1 antibodies or PD-L1 checkpoint inhibitors, modify the immune system so that it will respond to and attack cancer cells.

Drug Options

Several immunotherapies are currently approved for treating NSCLC. Nivolumab (Opdivo), pembrolizumab (Keytruda), atezolizumab (Tecentriq), and durvalumab (Imfinzi) interfere with PD-L1 action, while ipilimumab (Yervoy) interacts with the CTLA-4 receptor, another immune protein.

All of these drugs are given as intravenous (through the vein) infusions approximately every two to three weeks.

Drug Receptor
Nivolumab (Opdivo) PD-1
Pembrolizumab (Keytruda) PD-1
Atezolizumab (Tecentriq) PD-L1
Durvalumab (Imfinzi) PD-L1
Ipilimumab (Yervoy) CTLA-4

Nivolumab (Opdivo)

Opdivo is approved for treating a number of cancers, including metastatic NSCLC that has progressed during or after platinum-based chemotherapy.

In addition, Opdivo is the first immunotherapy approved for use before surgery for treatment of adults with resectable NSCLC, in combination with platinum chemotherapy.

Patients with NSCLC who have changes in the EGFR or ALK genes should have persistent tumor progression despite treatment with FDA-approved therapy that targets cancer with these genetic changes prior to starting Opdivo.

Opdivo is also approved in adult patients with metastatic NSCLC expressing PD-L1, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with Yervoy (ipilimumab).

Finally, it is approved in adult patients with metastatic NSCLC, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with Yervoy and platinum chemotherapy.

Opdivo is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, reducing the cancer-mediated inhibition of the immune system.

This drug was effective in improving the survival of patients in clinical trials prior to its approval and has also shown benefits in real-world use since its approval for NSCLC in 2018.

Dose for NSCLC: 240 milligrams (mg) every two weeks or 480 mg every four weeks

Pembrolizumab (Keytruda)

Keytruda can be used in combination with pemetrexed and platinum chemotherapy as a first-line treatment of patients with metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations. Keytruda is also approved as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. 

Keytruda has also been approved to treat advanced nonsquamous NSCLC lung adenocarcinoma along with chemotherapy, regardless of whether the tumor cells are PD-L1 positive.

Finally, it has been approved as first-line treatment in combination with chemotherapy for metastatic squamous NSCLC.

Keytruda promotes T-cell action against cancer cells by preventing the tumor's inhibition of the T-cell immune response. This monoclonal antibody prevents PD-L1 and PD-L2 from interacting with the PD-1 receptor by competitively binding with it.

Treatment with this medication is associated with longer survival of people who have advanced NSCLC.

Dose for NSCLC: 200 mg every three weeks

Atezolizumab (Tecentriq)

Tecentriq is FDA-approved as a single agent for the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

It is also approved in frontline treatment in combination with two different chemotherapy regimens (one containing Avastin/bevacizumab) for people who don't have EGFR or ALK genetic changes, and for the treatment of metastatic NSCLC with disease progression during or following platinum-containing chemotherapy.

When it's used for people who have EGFR or ALK genetic changes, disease progression must have occurred despite use of FDA-approved therapy for NSCLC with these genetic changes.

Tecentriq is a monoclonal antibody that binds to PD-L1 and blocks its interactions with PD-1 receptors in order to overcome the tumor-mediated inhibition of the body's anti-cancer immune response. This treatment has been shown to induce tumor shrinkage as well as improve survival and patient satisfaction when used in the treatment of NSCLC.

Dose for NSCLC: 1,200 mg IV over 60 minutes, followed by bevacizumab, paclitaxel, and carboplatin on the same day, every three weeks for a maximum of four to six weeks

Durvalumab (Imfinzi)

Imfinzi is approved for the treatment of unresectable stage III NSLC if the disease has not progressed after treatment with chemotherapy and radiation therapy.

Imfinzi is a monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (an immune protein).

In research trials, this medication improved progression-free survival and measurable aspects of quality of life for people with NSCLC.

Dose for NSCLC: 10 mg/kilogram (kg) every two weeks

Ipilimumab (Yervoy)

Yervoy is approved for the treatment of advanced NSCLC. It is taken along with nivolumab (Opdivo).

Yervoy is a type of immunotherapy that works differently than the other immunotherapies used to treat NSCLC. It is a monoclonal antibody that binds to the CTLA-4 receptor, which is located on the T-cells. Normally, CTLA-4 slows T-cell activation, and ipilmumab works by allowing T-cells to be activated against the tumor.

Dose for NSCLC: 3 mg per kg of body weight every three weeks, for a total of four doses

Side Effects

Immunotherapies used for NSCLC commonly cause side effects, although the effects tend to be milder than the side effects of chemotherapy and radiation therapy.

Day of Your Infusion

Immunotherapy medications can cause reactions during or within hours of an infusion in some people. An infusion reaction may involve one or more of the following:

  • Chills
  • Fever
  • Dizziness
  • Trouble breathing

Even if you haven't had an infusion reaction in the past, you can still develop one with future infusions.

Days After Infusion

Immunotherapies can also cause prolonged side effects that might not necessarily develop until days after the infusion.

Common side effects include:

  • Fatigue
  • Itching or skin rash
  • Diarrhea or constipation
  • Decreased appetite
  • Nausea
  • Fever
  • Cough

Complications and Concerns

Serious but uncommon complications of immunotherapy in NSCLC include:

Cancer pseudoprogression, a condition in which a tumor appears to be growing on imaging studies before it resumes its original size or shrinks, is possible and believed to happen due to the appearance of therapeutic inflammation.

On the other hand, sometimes hyper-progression can occur with immunotherapy. This is a situation in which the tumor actually does worsen, possibly as an adverse effect of the treatment.

It isn't possible to know whether an enlarging tumor is worsening or whether you are experiencing pseudoprogression until several months after treatment is complete.


According to the National Comprehensive Cancer Care Network guidelines for NSCLC, there are areas in which consensus regarding NSCLC treatment with immunotherapy has not yet been reached—including as it relates to possible contraindications.

Nevertheless, there are situations when immunotherapy has been shown to be problematic. These treatments might not be recommended if your risk of side effects exceeds the anticipated benefits of treatment.

Generally, immunotherapy drugs are not recommended as a treatment for NSCLC if the disease has not been treated with a trial of prerequisite first-line therapies first.

Additionally, immunotherapy might be harmful to your health if you are already immunosuppressed or have health problems like pneumonitis, hepatitis, or pituitary dysfunction.

A Word From Verywell

If you have been diagnosed with NSCLC, you and your healthcare providers will thoroughly review your treatment options. While several immunotherapeutic options are available, the treatment is new and emerging. You might consider enrolling in an NSCLC treatment clinical trial.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Colleen Doherty, MD
 Colleen Doherty, MD, is a board-certified internist living with multiple sclerosis.