Immunotherapies for Non-Small Cell Lung Cancer

Exciting treatments for those with advanced lung cancer

In This Article

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, doctors can select an immunotherapy drug that is designed to attack a patient's specific type of NSCLC in a more targeted way.

Some examples of immunotherapy drugs used for non-small cell lung cancer include Opdivo, Keytruda, and Tecentriq. Because of the way immunotherapies zero in on the cancer cells, immunotherapies like these often result in fewer and milder side effects than chemotherapy.

Antibodies attacking a cancer cell
Design Cells / Getty Images

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 pre-requisite medications, have been met.

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 PD-1 receptors on T-cells or the PD-L1 proteins on the cancer cells, although some interact with other receptors.

PD-1 binds to proteins on the surface of healthy cells, which prevents immune cells from attacking healthy cells. It is 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-1, which are called PD-1 antibodies or PD-1 checkpoint inhibitors, modify the immune system so it will respond to and attack cancer cells.

Drug Options

Several immunotherapies are approved for treating NSCLC. Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Durvalumab (Imfinzi) interfere with PD-1 action; Yervoy (ipilimumab) interacts with the CTLA-4 receptor, another immune protein.

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

Drug Receptor
Opdivo (nivolumab) PD-1
Keytruda (pembrolizumab) PD-1
Tecentriq (atezolizumab) PD-L1
Imfinzi (durvalumab) PD-L1
Yervoy (ipilmumab) CTLA-4

Opdivo (nivolumab)

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

Nivolumab 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

Keytruda (pembrolizumab) 

Keytruda is FDA-approved to treat advanced NSCLC. It can be used in metastatic nonsquamous NSCLC when there is no EGFR mutation or an ALK translocation and at least half of the tumor cells are positive for PD-L1. 

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.

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

Pembrolizumab 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

Tecentriq (atezolizumab)

Tecentriq is FDA-approved for the treatment of metastatic non-squamous NSCLC in combination with Avastin (bevacizumab), Taxol (paclitaxel), Abraxane (paclitaxel), or Paraplatin (carboplatin) for people who don't have EGFR or ALK genetic changes. It is also approved 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, it is only used if disease progression occurred despite use of FDA-approved therapy for NSCLC with these genetic changes.

Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interactions with PD-1 receptors and those of B7.1, a protein that activates the immune system, 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 it's used for the treatment of NSCLC.

Dose for NSCLC: 1200 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

Imfinzi (durvalumab)

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

Durvalumab 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/kg every two weeks

Yervoy (ipilimumab) 

Yervoy is approved for the treatment of advanced NSCLC. It is to be taken along with nivolumab.

Ipilimumab 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 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.

Contraindications

According to the National Comprehensive Cancer Care Network (NCCN) 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 pre-requisite 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 doctors 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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