For most lung cancer patients participating in immunotherapy clinical trials can be the best option. It gives them the opportunity to get access to the latest innovative treatments and a chance to advance the lives of other cancer patients as well.
Lately, the shift has focused on clinical trials that combine immunotherapy agents. The hope is that tweaking the immune system in more than one way will awaken it so that it recognizes and attacks cancer cells.
Read MoreImmunotherapy for Lung Cancer
“Immunotherapy is incredibly exciting for us because what it’s doing is allowing our white blood cells, your white blood cells to fight the cancer directly,” Dr. Kenneth Miller, director of outpatient oncology at the University of Maryland Greenebaum Cancer Center told SurvivorNet. “Typically, cancer has a protein on its surface that turns off your white blood cells.”And what we’re now able to do is to neutralize that so the white blood cells recognize the cancer.
Approved immunotherapeutic treatments for lung cancer include:
Immune checkpoints inhibitors. These are proteins that inhibit cancer cells from tricking immune cells into thinking they are normal cells. Generally, immune cells can differentiate between normal cells and foreign cells through the presence of a checkpoint.
These checkpoints are only present in normal cells. The way this works is that immune cells do their normal surveillance, and when they see these checkpoints on normal cells, they bind to them, and their attacking ability is switched off. Now in case, this is a cancer cell, the immune cell will not find the checkpoint and will immediately destroy it to protect the body.
However, some cancer cells can fool immune cells by carrying these checkpoints as well on their surface, switching them off, which in turn makes the immune cells unable to recognize and kill the cancer cells.
For this problem, immune checkpoint inhibitors are the solution where they can bind to and block the specific checkpoints either on the normal or cancer cells, making them unable to bind, which in turn boosts the surveilling function in immune cells to find and destroy the cancerous cells.
Checkpoint inhibitors for lung cancer include:
- Nivolumab (Opdivo), pembrolizumab (Keytruda), and cemiplimab (Libtayo) and these target PD1 protein in the immune cells
- Atezolizumab (Tecentriq) and durvalumab (Imfinzi) target PD-L1 on the cancer cells
- Ipilimumab (Yervoy) which targets CTLA4 protein on the immune cells
Monoclonal antibodies. These are antibodies (proteins) that target specific other proteins (antigens) responsible for functions in the cell that may go haywire and increase uncontrollably when the normal cells turn into cancerous cells.
Monoclonal antibodies can function through different modalities. The first one can be by loading them with a toxic drug to directly target the mutated (changed) protein causing the cancer, and the second modality can be by targeting while inhibiting the growth of the cancer by binding to its nutritional source, and the third and final modality can occur by binding to the protein and inhibiting its growth.
In the end, all modalities will result in stopping the cancer from growing, provided of course, that the protein causing the cancer is identified beforehand.
Approved monoclonal antibodies drugs for lung cancer treatment are:
- Bevacizumab (Avastin)
- Ramucirumab (Cyramza)
The mechanism of action for these drugs is that they stop the growth of cancer cells by inhibiting their nutritional source. They bind to VEGF ligand, which, is a type of protein responsible for the growth of blood vessels surrounding the cancer cells. By inhibiting their growth, they will be starved until they shrink and die.
Current research is still being done on other immunotherapies for lung cancer treatment through clinical trials pending FDA approval.
Side Effects of Immunotherapy
As with any treatment option, there are some advantages and disadvantages. Here are some of the side effects of immunotherapy you should keep in mind:
Not everyone will find it effective. When immunotherapy works, it can significantly improve outcomes and help patients live longer, it doesn't work for everyone. We are not sure why this happens, but it seems that only half the people who tried it gained its benefits.
It can take a long time to work. Sometimes, immunotherapy doesn't work right away; it takes a considerable amount of time compared to other treatments.
Resistance. Over time, your body can get used to the treatment, and it's not effective anymore. So, even if it worked initially and your tumor starts getting smaller, it can stop working, and your cancer can grow again.
Allergic reaction. You can have some side effects from the place the drugs are administered, like itching, rash, or bleeding.
Autoimmune reaction. this is a serious side effect where your immune system can go into overdrive and start attacking your own healthy organs. Often, any damage caused to endocrine cells is permanent.
Other side effects. Some less serious side effects include flu-like symptoms ranging from fatigue, nausea, fever, diarrhea, and others that differ from one patient to another.
Currently, there are many trials and research into how to avoid these side effects and make immunotherapy a more effective treatment for lung cancer. A trial led by Dr. Leena Gandhi, Director of the Center for Cancer Therapeutic Innovation, indicated that survival odds could go up for people with the most common type of lung cancer if they are given an immunotherapy drug called Keytruda plus chemotherapy.
She shared her thoughts with SurvivorNet, claiming that people participating in the trial had advanced stages of non-squamous non-small cell lung cancer, and while chemotherapy alone didn't have great treatment outcomes, the combination of chemotherapy and Keytruda showed a significant improvement.
Dr. Gandhi called it "a sea change in the way we think about treating lung cancer."
Combining Therapies What Does It Mean For Lung Cancer Patients?
Another combination of immunotherapy drugs Opdivo (nivolumab) and Yervoy (ipilimumab) is approved for first-line treatment of some metastatic or recurrent non-small cell lung cancers.
With that in mind, combining treatments, whether it's immunotherapy and chemotherapy or two immunotherapies, may be an option for certain patients with lung cancer.
The advent of combining therapies for lung cancer is that it can work on increasing the efficacy, fixing resistance issues, and treating those difficult cases in their metastatic stage. Even though there haven't been many approvals on that front, immunotherapy clinical trials are underway to figure out how to better treatment results in the future.
Dr. Gandhi says "Many of the trials that we are currently doing are combinations of immunotherapy – is that if we worry a patient is less likely to respond to immunotherapy by one immunotherapy by itself, can we stimulate the immune system in two different ways and get a better chance that way? "
Eligibility Criteria For Immunotherapy Clinical Trials
Your eligibility will be assessed by your doctor, but generally, since immunotherapy cancer clinical trials depend on a functioning immune system, you can be disqualified if you have any of the following health conditions:
- If you have an autoimmune disease (with some exceptions of relatively feeble conditions like vitiligo)
- Splenectomy (if you had your spleen removed)
- Immunosuppression (whether this is because of a disease like HIV or from using medication)
- Those who can't perform well on their own physically (unless the aim of the trial is specifically for that)
- Those with a short life expectancy
- Serious heart disease or conditions
- Chronic infections (Like hepatitis or HIV)
- History of a prior cancer
These parameters are all interchangeable according to the inclusion and exclusion criteria set by the principal investigator and the research team conducting the trial.
The Bottom Line
Immunotherapy is a type of cancer treatment that uses the body’s immune system to fight cancer. There are different types of immunotherapy, and each type can be used alone or in combination with other treatments.
Some of the most common types of immunotherapy used to treat lung cancer are immune checkpoint inhibitors. Additionally, different combinations of treatments remain an active area of research and the search continues for new potential candidates that are safe and effective.
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