Immunotherapies for Non-Small Cell Lung Cancer

Exciting treatments for those with advanced lung cancer

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Immunotherapy is a method of medical treatment that modifies some aspects of the body's immune system to help manage a number of illnesses, including non-small cell lung cancer (NSCLC). Each type of cancer that can be managed with this treatment approach utilizes only the immunotherapy drugs that target distinct molecular features of that specific type of cancer. Because it is targeted in its action, immunotherapy often results in fewer and milder side effects than chemotherapy.

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. For this type of cancer, immunotherapy may be used in combination with chemotherapy, radiation therapy, and/or surgery. Immunotherapy in NSCLC works by modifying the action of immune system checkpoints.

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.

PD-1

One major immune system checkpoint targeted by NSCLC immunotherapies is PD-1, a receptor on the T-cells that binds to proteins on the surface of healthy cells. The binding of PD-1 prevents these immune cells from attacking the healthy cells.

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.

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

Types

Several immunotherapies are approved for treating NSCLC. Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Durvalumab (Imfinzi) interfere with PD-1 action, and 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
Opidvo (nivolumab) PD-1
Keytruda (pembrolizumab) PD-1
Tecentriq (atezolizumab) PD-L1
Imfinzi (durvalumab) PD-L1
Yervoy (ipilmumab) CTLA-4

Opidvo (nivolumab)

Opidvo 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 Opidvo.

  • The dose of Opidvo for NSCLC is 240 mg every 2 weeks or 480 mg every 4 weeks.

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-medicated 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 practice since its approval for NSCLC in 2018.

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.

  • Keytruda is dosed at 200 mg every 3 weeks.

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

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

Tecentriq (atezolizumab)

Tecentriq is FDA approved for the treatment of metastatic non-squamous NSCLC in combination with bevacizumab, paclitaxel, and 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 FDA-approved therapy for NSCLC with the genetic changes.

  • Tecentriq is given at a dose of 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.

Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interactions with PD-1 receptors and B7.1 (a protein that activates the immune system) receptors to overcome the tumor mediate inhibition of the body's anti-cancer immune response. This treatment has been shown to induce tumor shrinkage and improve survival and patient satisfaction when it's used for the treatment of NSCLC.

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.

  • Imfinzi is used at a dose of 10 mg/kg every 2 weeks.

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 has improved progression-free survival and improved measurable aspects of the quality of life for people with NSCLC.

Yervoy (ipilimumab) 

Yervoy is approved for the treatment of used for advanced NSCLC, along with nivolumab.

  • Yervoy is used at a dose of 3 mg per kg of body weight, given IV over 90 minutes every 3 weeks for a total of 4 doses.

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.

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.

These medications can cause reactions during or within hours of the infusion. An infusion reaction may consist of chills, fever, dizziness, and/or trouble breathing. You might not experience an infusion reaction, and if you haven't had one with a previous infusion, you can still develop these symptoms with future infusions.

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

Immunotherapies also can cause cancer pseudoprogression, a condition in which the tumor that is improving with treatment appears on imaging studies to be growing. This is believed to occur due to the appearance of therapeutic inflammation.

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.

Serious, but uncommon, side effects of immunotherapy in NSCLC include pneumonitis (inflammation of the lungs) and hepatitis (inflammation of the liver), and pituitary dysfunction.

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 proposed contraindications.

Nevertheless, there are situations when immunotherapy can 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 discuss your treatment options. There are a variety of treatments for NSCLC, and immunotherapy might be part of your treatment regimen. Your treatment may include surgery, chemotherapy, radiation, and immunotherapy. At this time, immunotherapy isn't considered suitable as the only treatment for NSCLC and it is used along with other treatment strategies.

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