What is Immunotherapy for Cancer?
The immune system uses its white blood cells to attack cells in the body that are abnormal or foreign. Cancerous cells have the ability to prevent the immune system from doing its job. The cancer produces certain proteins to protect the tumor from white blood cells. As a result, the body does not recognize the tumor as abnormal. Immunotherapy drugs stop this from happening and ensure the white blood cells recognize the cancer cell properly and attack it. The cancer cells themselves are not necessarily difficult to fight. However, they continue to divide rapidly. So, immunotherapy drugs help a patient's immune system control their cancer on its own before it can spread.Immunotherapy for Lung Cancer Who is a Candidate?
Unfortunately, immunotherapy does not work for every patient. It was initially only used for very advanced stages (Stage IV). However, it is becoming more commonly used as a treatment option in earlier disease progression (Stage III). Immunotherapy treatments are being used in non-small cell lung cancer (NSCLC) stages three and four, as well as in extensive stage small cell lung cancer (SCLC). When first approved, immunotherapy was only used in patients who had failed other treatment options, but now it can be part of one's initial treatment as long as the disease is at an advanced stage (stages III or IV). The type of cancer and the specific way the cancer interacts with the immune system determines whether immunotherapy is a viable option. Genetic testing for the expression of certain immune proteins is also essential to determine if a patient is likely to respond well to this type of treatment option.
Genetic Testing – Immunotherapy for Lung Cancer
Read MoreImmunotherapy Treatment Options
Immunotherapy alone can be a valuable option in treating stage four lung cancer. It is also sometimes used in combination with other treatment options, such as radiation and chemotherapy.Checkpoint Inhibitors
This category of medications includes the most common immunotherapy agents approved for lung cancer. Checkpoint inhibitors can be used in combination with chemotherapy or radiation or after recurrence has occurred following traditional treatment options. Some patients may also receive multiple checkpoint inhibitors concurrently (at the same time). Several studies have shown improvements in survival with checkpoint inhibitors when used alone or in combination with traditional treatments.How Do They Work?
Our immune cells have proteins on their surfaces that interact with proteins in normal, healthy cells. These proteins have the ability to either start or stop an immune response, earning the name 'checkpoint proteins.' Cancer cells will mimic these checkpoint proteins to protect themselves from being attacked by immune cells. Checkpoint inhibitors target these proteins in cancer and immune cells.
PD-1 and PD-L1 are checkpoint proteins. PD-1 is found in the body's immune cells, and PD-L1 is found in cancerous and immune cells. Both of these proteins are targets. Using medications to interfere with how these proteins interact helps keep the immune response 'turned on.' By doing so, the immune system will recognize and fight the cancer cells. Levels of PD-L1 in the cancer cells should be tested prior to starting these therapies. The medication is more likely to be successful if a patient has a high expression of this checkpoint protein. Some PD-1/PD-L1 inhibitors, which are given by intravenous (IV) infusion, include the following:
- atezolizumab (Tecentriq®)
- cemiplimab (Libtayo®)
- durvalumab (Imfinzi®)
- nivolumab (Opdivo®)
- pembrolizumab (Keytruda®)
CTLA-4 is another checkpoint protein that, when blocked, 'turns on' the immune response and encourages the immune cells to attack the cancer cells. The only FDA-approved CTLA-4 inhibitor for lung cancer includes the following:
- ipilimumab (Yervoy®)
Side Effect Profile?
Common side effects of PD-1/PD-L1 inhibitors include fatigue, itchy skin, nausea, constipation, colitis, diarrhea, muscle or bone pain, and decreased appetite. More severe symptoms include inflammation of different organs, such as the liver or thyroid. Some symptoms may occur only during or shortly following drug administration, while others may become chronic complications. They can be managed with either over-the-counter or prescription medications. Be sure to consult with your doctor for more information.
As mentioned, an infusion reaction during administration is possible with these medications, especially the first time it is received. Because of this, the first infusion of the drug may be given at a slower rate than subsequent infusions. An infusion reaction has similar symptoms to an allergic reaction and can include the following: flushing, rashes, chills, and trouble breathing. Patients should be watched very closely during their first infusion of these drugs.
Sometimes, these medications can also cause the immune system to start fighting the healthy tissue of other organs in an autoimmune response. Any new symptom should always be discussed with your physician. There is a significant risk of side effects with any cancer treatment. In general, immunotherapy medications have fewer side effects than traditional treatments.
Lung Cancer Vaccinations
How Do They Work?
There are lung cancer vaccinations currently in clinical trials. These vaccines aim to target proteins in cancerous cells and help the immune system become better at recognizing and fighting them. Lung cancer vaccines can be used to stop a tumor from growing by making sure all cancerous cells are gone, following a more traditional treatment. There are no FDA-approved cancer vaccines available in the U.S. today. However, there are several that are ongoing clinical trials with the hope of gaining market approval in the near future. One vaccine, CIMAvax-EGF, causes the body to make anti-EGF antibodies, which then cause the immune system to decrease the amount of EGF in the blood. The cancer cells that relied on EGF to grow and spread would be prevented from doing so.
In trials, patients that received four intramuscular (IM) injections of the vaccine following 4-6 cycles of chemotherapy had improved overall survival. Patients that had a large expression of the EGF protein before treatment started had more success with the vaccine. It is already being used to treat lung cancer in Cuba, while U.S. studies are ongoing. Currently, there is a clinical trial for CIMAvax-EGF based out of Roswell Park Comprehensive Cancer Center in Buffalo, NY.
Side Effect Profile?
Redness, itching, or swelling at the injection site, also called an injection site reaction, is the most common side effect. Headache, nausea, vomiting, fever, and chills are commonly found as adverse effects of cancer vaccines.
Monoclonal Antibodies
How Do They Work?
Monoclonal antibodies mimic the way antibodies work in the body. They can either kill the cancer cells directly or prime the immune response to fight the cancer itself. Some monoclonal antibodies that interfere with VEGF are used in the treatment of lung cancer. VEGF is a protein that allows for the creation of new blood vessels. These medications prevent the cancerous cells from being able to grow new blood vessels, and this essentially starves the cancer cells as they cannot get the necessary nutrients to survive. There are two of these therapies approved for lung cancer treatment. They are both given by IV infusion and include the following:
Side Effect Profile?
Injection site reactions, similar to checkpoint inhibitors, are common side effects seen with monoclonal antibodies. They also may cause flu-like symptoms such as fever, chills, muscle aches, nausea, vomiting, and fatigue. Monoclonal antibodies can also cause changes in blood pressure, mouth and skin lesions, and cardiovascular complications.
CAR T-Cell Therapy
CAR T-cell therapy is not yet approved for lung cancer, but clinical trials are currently ongoing. It is, however, approved for several blood cancer types. This therapy comes with significant risks, but if successful, it often leads to remission without further treatment.
How Does it Work?
T-cells are one of the main cell types in the immune system. For this type of therapy, the T-cells are removed from the body during a process called plasmapheresis. The cells are sent away to a lab where they are treated with certain chemicals to 'prime' them to kill cancer cells. The T-cells become CAR T-cells after this treatment. This process can take several weeks. During this time, patients are sometimes given a few doses of chemotherapy to prevent the tumor from growing and decrease the immune system, allowing CAR T-cells to do their job. The patient's CAR T-cells are then put back in the body and begin attacking the cancer. In the weeks that follow, patients are typically asked to stay close to a hospital. There are daily checkings of vitals and overall status because it is common for patients to have an associated immune reaction.
Side Effect Profile?
Cytokines, which are chemicals that are part of our natural immune response, are released in large numbers when the CAR T-cells begin to fight the cancer. These cytokines cause symptoms such as trouble breathing, fever, chills, fast heartbeat, nausea, vomiting, diarrhea, and pain. More serious nervous system complications such as stroke, seizures, loss of consciousness, and confusion can also occur. Patients are often given anticonvulsant medications for several months following their CAR T-cell treatment to prevent the occurrence of seizures.
Due to a decreased immune system, patients are also especially susceptible to infection. The impact of T-cell therapy on routine immunizations is unknown. If possible, after CAR T-cell therapy is complete, patients should be tested for antibody levels to evaluate if any immunizations need to be re-administered accordingly.
Resistance to Immunotherapy Treatments
Resistance to immunotherapy medications is common and falls into two categories: primary and acquired. Primary resistance is when the tumor does not initially respond to the treatment. In this case, the patient would need to change their course of treatment.
Acquired resistance, however, refers to when treatment was working, but now there has been additional tumor growth, relapse, or metastasis. The expression of proteins can change easily. With that being said, either cancer or immune cells have the potential to change their characteristics, which may make treatments less effective. In almost all cases, acquired resistance occurs eventually, but immunotherapy may control the cancer successfully for years and beyond.
These treatments can only be given for a maximum of two years, but the benefit of the drug may last much longer. In other words, just because the medication is stopped at the two-year mark does not mean that the cancer immediately begins to grow again.
Benefits of Immunotherapy for Lung Cancer
Immunotherapy does not work for everyone. The treatment is estimated to be successful in about 25%-35% of patients. For the patients that are in this group, immunotherapy works really well. It only takes a few months or so to know if the treatment is going to be able to manage the disease.
The primary benefit of using immunotherapy for lung cancer is that there is less damage done to healthy cells. This is because the body's natural defense, the immune system, is trained to fight the cancer, rather than using systemic chemicals, such as chemotherapy treatment. Traditional treatments, such as chemotherapy, may also work better if the patient has received some immunotherapy treatment. Most patients do not see complete cancer eradication with immunotherapy. But the cancer does stop growing, allowing them to live longer.
Between 2014-2018, the decrease in the lung cancer death rate was responsible for almost half of the overall cancer death rate decrease. This may be due, in part, to new immunotherapy treatments being more widely utilized. Immunotherapy treatments are still being studied but show great promise in helping patients like you control and manage the progression of advanced lung cancer and ultimately improve survival.
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