Guide to Late-Stage Lung Cancer Immunotherapy Options

"I am more hopeful when I am able to use immunotherapy, and the reason for that is we are seeing people live out four to five years. In the big scope, it does not sound like a lot; but in lung cancer, it is a big advance," Dr. Mohana Roy, clinical assistant professor at Stanford University School of Medicine, tells SurvivorNet.

Immunotherapy, including checkpoint inhibitors, is already making a difference in patient's treatment who suffer from advanced stage lung cancer. See how this type of therapy is making waves in modern oncology treatment decisions and ultimately patient survival rates.

Late Stage Immunotherapy as a First Line Treatment

The Immunotherapy Revolution

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Chemotherapy and radiation therapy used to be the traditional backbone of treatment for late stage lung cancer. These treatments kill cancer cells by the means of strong medicine and high doses of radiation. Immunotherapy is different, to say the least. It harnesses the power of your immune system to target your cancer. "Immune therapies are medications that enhance the immune response toward the cancer," Dr. Roy says.

Today, immunotherapy is almost always a first treatment for late stage lung cancer, she adds. The exception is if you have a gene mutation, such as ROS, ALK, and EGFR. In that case, you will instead most likely get a treatment targeting that specific mutation.

Checkpoint Inhibitors

When doctors recommend immunotherapy for lung cancer, they are usually referring to checkpoint inhibitors. Generally speaking, checkpoint inhibitors stop checkpoint proteins from binding to other proteins.

"What happens is that our systems or immune systems are geared to have various turning off points, various ways in which the immune system when it detects something that could be a potential threat, can be turned off or dialed down," Dr. Elad Sharon, a senior investigator in the Investigational Drug Branch of the National Cancer Institute Cancer Therapy Evaluation Program, tells SurvivorNet.

Here is how they work:

• Checkpoints are proteins on T cells, which is a type of immune cell. T cells attack harmful substances such as bacteria, viruses, and even cancer cells. PD-1 is an example of a checkpoint found on this type of immune cell.
• Lung cancer cells come equipped with their own protein, known as PD-L1. It tells the T cell, "Ignore me, I'm not doing anything wrong," Dr. Roy explains. "I think of it as a cloak that makes it hide from the immune system."
• The PD-1 to PD-L1 interaction turns the immune system 'off', allowing cancer cells to hide. When interaction is blocked by either PD-1 or PD-L1 inhibitors, suddenly the negative switch is turned off and the immune system can begin destroying and ultimately killing cancer cells.

One group of checkpoint inhibitors block PD-1. This essentially flips the switch 'on' T cells to unleash them on the cancer.

Examples of PD-1 inhibitors include the following medications:

• Cemiplimab (Libtayo®)
• Nivolumab (Opdivo®)
• Pembrolizumab (Keytruda®)

Another group of checkpoint inhibitors targets PD-L1 to help the immune system recognize the cancer.

PD-L1 inhibitors include the following medications:

• Atezolizumab (Tecentriq®)
• Durvalumab (Imfinzi®)

Could Late Stage Immunotherapy Help You Live Longer?

Studies show that lung cancer responds well to immunotherapy. When checkpoint inhibitors are given as a first-line treatment or after other treatments have not shown any benefit, they help some people survive longer. These drugs may also improve progression-free survival, which means living for a longer period of time without your cancer growing or progressing.

Some study results have been dramatic. For example, in a five-year study of Keytruda, the drug doubled overall five-year survival rates from 16.3% to 31.9% compared to chemotherapy.

The trouble is, however, that these treatments do not work for everyone. Remember, treating cancer is not "one size fits all". Currently, doctors use biomarkers substances in the blood or on the tissues obtained from biopsy to identify the best candidates for this treatment.

Are You a Good Candidate for Late Stage Immunotherapy?

To determine if immunotherapy is the right treatment option for you, here is what will happen:

• Your doctor will likely test your tumor's PDL-1 level when you have a biopsy. If your tumor has a high PDL-1 level, you may be able to get immunotherapy alone. If it is low or you have a lot of symptoms, you may get chemotherapy too", Dr. Roy says.
• The results of a PDL-1 test are sometimes reported as a score, which represents the percentage (%) of cancer cells that test positive for PDL-1. The higher your score, the more likely that immunotherapy is a good treatment approach for you.

But it is important to keep in mind that not everyone who tests positive for PDL-1 will be a good candidate for an immunotherapy drug and that your response to this test has the potential to change over time.

Other forms of checkpoint inhibitors exist and continue to be a focus of study in the realm of oncology. For example, Ipilimumab (Yervoy®) is another kind of checkpoint inhibitor. It targets a protein called CTLA-4, which is found on the surface of T cells. Yervoy® is used together with Opdivo® to treat advanced stage lung cancer.

Stages of Grief If You are Not a Good Candidate

As mentioned above, certain immunotherapies, along with other treatment options, may not be the best treatment option for you. This may not be the news you wanted to hear from your oncologist. Remember, it is not always easy digesting your diagnosis, survival rate, or treatment options. Although you may feel angry, depressed, or sad if current treatments are not applicable to you or a feeling of hopelessness sinks in, these are all normal stages of grief. However, it is important to ultimately accept these challenges that have been presented and make an action plan with your oncology team to get you on track to better health. The future of cancer treatment is hopeful, so you should be too!

The Potential for Side Effects

Chemotherapy side effects, such as nausea and hair loss, can be tough. But they are pretty predictable by now. Checkpoint inhibitor side effects are a bit trickier to predict.

Dr. Roy says about nine out of every ten of her patients feel fine on these medications. "The 10 percent is where we run into trouble," she adds.

The most common side effects include the following:

• Fatigue
• Rashes
• Diarrhea
• Weakness
• Headache
• Impaired thyroid function

The biggest worry is that by unleashing the body's immune system, this treatment might trigger damaging inflammation. Essentially, your body could start to attack its own organs, which would be troublesome, to say the least. If this happens, the side effects are often irreversible and you may have them for life.

"You do not know who it will affect and who it will not," Dr. Roy says. "When I start someone on immunotherapy, I say, 'Anything weird, I need to know about it.'"

If you suffer from baseline autoimmune problems, you might have a flare-up of your condition. You should carefully discuss with your doctor how to use these drugs safely.

On the Horizon What's Next

Several new immunotherapies are working their way through clinical trials, which is a major step in the right direction for expanding treatment options. Some studies are looking at various different checkpoint targets. "The more checkpoints we are able to target, I think we will have more durable responses," Dr. Roy says.

Cancer vaccines are another investigational immunotherapy. Just as a vaccine for the flu or COVID-19 generates an immune response against a virus, these vaccines would trigger an immune response against cancer. This may be the future of cancer treatment and prevention as we know it.

Exploring Future Treatments in Clinical Trials

Enrolling in a clinical trial could give you access to these and other emerging lung cancer immunotherapies before they have gained market approval by the Food and Drug Administration (FDA). If you do want to try a study, Dr. Roy advises going into it with a realistic understanding of what it can and cannot do for you.

The treatments being tested in studies, while promising, do not always work. "One thing I always try to make clear is that clinical trials, while they can help the patient themselves, are meant to promote science and help others," she cautions.

For more information on clinical trials and enrollment opportunities, be sure to visit ClinicalTrials.gov, which is a helpful resource provided by the U.S. National Library of Medicine.

Be Hopeful for Late Stage Immunotherapy for Lung Cancer

We still do not have a cure for late stage lung cancer. But thanks to immunotherapies and other novel new treatments, it is becoming a more manageable disease with a more positive outlook. "We hope people can at least live out [for a few years] and do the things they want to do," Dr. Roy says. Currently, increasing a patient's survival rate and quality of life is of utmost importance until a cure is found.

What to Ask Your Doctor Moving Forward

• Should I have genetic or molecular testing done?
• Do I have any genetic mutation that would change the course of my treatment?
• Am I eligible for immunotherapy? Am I more, or less, likely to respond to this treatment?
• How aggressively should we treat my cancer?
• Is there a clinical trial that would be relevant for me? If so, how can I participate?

Final Thoughts

Immunotherapies have become a great option for late stage non-small cell lung cancer (NSCLC), including squamous cell lung carcinoma, adenocarcinoma, and large cell carcinoma, as well as small-cell lung cancer (SCLC), which includes oat cell cancer and combined small cell carcinoma. With the progression of clinical trials and the identification of new checkpoint targets, the future is bright for new agents coming to market. With that being said, it is important to remember that these new and exciting treatment options may not be right for everyone. Your dedicated oncology team does not want to put you at risk of unwanted side effects or your immune system attacking itself. The benefits must always outweigh the potential risks. Be sure to ask your oncologist(s) if immunotherapy is right for you and what tests need to be performed to ensure this.

 

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