Immunotherapy for Lung Cancer: For Patients

Since the first immunotherapy for lung cancer was FDA-approved in 2015, many lung cancer patients have benefited from this type of treatment. Immunotherapies help a person’s immune system eliminate or control cancer. We normally think about the immune system fighting infections caused by foreign invaders like viruses and bacteria. The immune system also recognizes that cancer cells are not normal. While the immune system is able to target and kill cancer cells, tumors can also develop ways of hiding from the immune system. Immunotherapies help the immune system recover its ability to fight cancer. For lung cancer patients, immunotherapy can help shrink tumors, prevent cancer recurrence after other treatments, and change active cancer into a more controllable disease.

The two main types of immunotherapies for non-small cell lung cancer (NSCLC), the most common type of lung cancer, are PD-1/PD-L1 inhibitors and CTLA-4 inhibitors. These immunotherapies are also referred to as immune checkpoint inhibitors.

Immunotherapy is an important option for NSCLC patients to consider since most NSCLC patients are not good candidates for targeted therapy. Targeted therapies are therapies that interfere with certain proteins that help cancer cells grow and spread but most NSCLC tumors do not have the biomarkers that current targeted therapies home in on.

Patients with NSCLC routinely receive immune checkpoint inhibitors along with other treatments. The exact treatment plan differs for each patient, mainly depending on the results of tumor biopsy testing, the extent of disease, and the characteristics of the cancer cells that a pathologist sees under a microscope.

How do immune checkpoint inhibitors work?

PD-1 and PD-L1 stand for programmed death 1 and programmed death ligand 1. CTLA-4 stands for cytotoxic T-lymphocyte-associated antigen 4. Both PD-1 and CTL-4 are proteins on the surface of T cells that act as control switches for the immune system. A complex system of multiple control switches receiving positive and negative signals lets the immune system know to attack abnormal cells and pathogens and to leave normal tissues in your body alone.

Proteins like PD-1 and CTL-4 are part of a system of immune checkpoints that when switched off prevent T-cells from reacting against normal cells in the body. Some tumor cells that should be recognized by T-cells display molecules on their surface that turn off the PD-1 and CTLA-4 immune checkpoint switches on T-cells. This suppresses the immune response to the tumor. Immune checkpoint inhibitors prevent cancer cells from turning off the T-cell response through the PD-1 and CTLA-4 immune checkpoints. This keeps T-cells more active.

Immune checkpoint inhibitor drugs are monoclonal antibody drugs. Monoclonal antibody drugs act like natural antibodies but are designed to stick to designated targets. Immune checkpoint inhibitors used to treat NSCLC are antibodies that stick to CTLA-4 and PD-1 immune checkpoint switches and prevent them from being switched off.

Another immune checkpoint inhibitor used for NSCLC blocks PD-L1, a protein on the surface of tumor cells, which interacts with PD-1 of T-cells turning off the PD-1 immune checkpoint switch. PD-1 and PD-L1 inhibitors are grouped together because both of these treatments block the same immune checkpoint.

Immune checkpoint inhibitors that target PD-1 and PD-L1 are more likely to work if the patient’s tumor has high levels of PD-L1. PD-L1 levels can be checked via tumor biopsy. PD-1 or PD-L1 inhibitor therapies may be used as a monotherapy when the tumors have high levels of PD-L1. Laboratory results that give a value above 50 percent are considered high levels. This means that more than 50 percent of the cells had PD-L1. People who have less than 50 percent of cells with PD-L1 are recommended to have a combination of immune checkpoint inhibitors and chemotherapy.

How are immune checkpoint inhibitors administered?

Immune checkpoint inhibitors are given by intravenous (IV) infusion every 2, 3, 4, or 6 weeks depending on which immune checkpoint inhibitor drug is used. Different combinations of immune checkpoint inhibitor drugs may be recommended depending on the stage of lung cancer. Other treatments such as chemotherapy may be given at the same time.

Immune checkpoint inhibitors are usually continued until the disease progresses or unacceptable toxicity occurs. Clinical studies suggest that continuation of immune checkpoint inhibitor treatments beyond one year is beneficial. Continued benefits have been reported after ending immunotherapy. More research is needed to determine the optimal duration of treatment. People can receive immunotherapy for a duration of years and experience fewer side effects than those undergoing chemotherapy or radiation therapy.

Immunotherapy for various types of NSCLC

FDA-approved immune checkpoint inhibitor treatments are available for various stages and types of NSCLC. Based on how cancer cells appear under the microscope, NSCLC is subdivided into squamous or non-squamous. PD-1 inhibitor therapy is an FDA-approved frontline treatment for metastatic non-squamous NSCLC in combination with chemotherapy. Patients with advanced squamous NSCLC and non-squamous NSCLC who have disease progression after standard platinum-based chemotherapy can receive an FDA-approved PD-1 inhibitor treatment. Several immune checkpoint inhibitor therapies are in clinical trials in different combinations with chemotherapy for different stages and types of NSCLC.

PD-1 inhibitor treatments are used for early-stage NSCLC as a first treatment or neoadjuvant treatment before surgery. People with metastatic NSCLC may receive a PD-1/PD-L1 inhibitor treatment alongside chemotherapy as a first treatment. PD-1/PD-L1 inhibitor treatments may be used for certain types of advanced NSCLC when cancer recurs after chemotherapy or other treatments.

Patients with stage III NSCLC who are not able to have surgery or chemotherapy with radiation may have PD-1 inhibitor therapy as a first treatment. PD-L1 therapy may be used to prevent cancer progression in patients with stage III NSCLC when their cancer cannot be removed with surgery in cases where it has not worsened after chemoradiation treatment. Patients with stage II or early-stage III NSCLC may receive PD-L1 inhibitor therapy after surgery along with chemotherapy to prevent cancer from recurring.

CTLA-4 inhibitor treatments may be part of the first line of treatment for NSCLC. CTLA-4 inhibitors are always given along with a PD-1 inhibitor and often with chemotherapy as well.

Immunotherapy side effects

Side effects of PD-1/PD-L1 inhibitor treatments include fatigue, cough, nausea, itching, skin rash, loss of appetite, constipation, joint pain, and diarrhea. For CTLA-4 inhibitor treatments, fatigue, diarrhea, skin rash, itching, muscle or bone pain, and belly pain are the most common side effects. CTLA-4 inhibitors are associated with more serious side effects compared with PD-1 and PD-L1 inhibitors. There is an increased risk of lung damage when administering immunotherapy to patients who have received or are concurrently receiving certain targeted therapies. Drugs given by IV may cause an infusion reaction which, similar to an allergic reaction, includes symptoms such as fever, chills, flushing or rash on the skin, wheezing, or trouble breathing.

Both classes of immune checkpoint inhibitors can cause autoimmune reactions. By making the immune system more active there is a risk that it may attack normal cells in the body. Because autoimmune reactions can cause life-threatening conditions it is important for patients on immune checkpoint inhibitor therapies to report new side effects to their healthcare team as soon as possible. If severe autoimmune reactions occur, your doctor may stop the treatment or prescribe high doses of corticosteroids to suppress your immune system.

Resistance to immune checkpoint inhibitors

Over time many patients with lung cancer develop resistance to immune checkpoint inhibitors. This means that a lung cancer patient may initially respond well to treatment and then later the treatment may stop working. Patients with NSCLC who have acquired resistance to PD-1/PD-L1 inhibitors and have had cancer progression may be offered chemotherapy.

If NSCLC has progressed several months or years after the last dose of PD-1/PD-L1 inhibitor, the patient may attempt to restart immunotherapy. Sometimes NSCLC will progress only in one or two tumor sites. In this case, patients may be recommended to have a therapy such as radiation, thermal ablation, or surgery directed at those sites while maintaining PD-1/PD-L1 inhibitor treatment.

Lung cancer treatment vaccinesLung cancer vaccines are treatment vaccines that increase the activity of the immune system against tumors or prevent tumors from returning. Cancer treatment vaccines work by telling the immune system to be on the lookout for certain cancer-specific antigens, molecules on the surface of cancer cells that are not found on healthy cells. There are currently no FDA-approved lung cancer vaccines but these treatments are being tested in clinical trials.

CAR-T therapy for lung cancer

CAR-T therapy is the delivery of immune cells called chimeric antigen receptor (CAR) T cells into the patient. CAR-T cells are T cells that are engineered from the patient’s own T cells or from a donor and then infused into the patient. The engineered T cells bind to targets on cancer cells and kill them. Currently, CAR-T therapies are only FDA-approved for blood cancers, but lung cancer CAR-T therapies are in clinical trials.

Conclusion

FDA-approved immunotherapy drugs for lung cancer are in the category of immune checkpoint inhibitors. Different immune checkpoint inhibitor treatment regimens and other types of immunotherapies are being tested in clinical trials for lung cancer. Patients with NSCLC should discuss immunotherapy options with their doctor. It is important to know that not all lung cancers respond well to immunotherapy. While it is difficult to predict how each person will respond your doctor can help you decide if immunotherapy might be right for you.

myTomorrows is dedicated to helping patients with lung cancer find lung cancer clinical trials. You can also find out more information by reading our guide on inoperable lung cancer.