New Data at ASCO: Encouraging Results For Immunotherapy in Advanced Non-Small Cell Lung Cancer

"These results speak to how we have really changed the way we treat lung cancer," Dr. Roy Herbst, head of the Clinical Research Program in Thoracic Oncology at Yale Cancer Center, told SurvivorNet. "It tells patients that if you get on this drug and you benefit, you will benefit from a long period of time. It shows there is hope." If you or your loved one has been diagnosed with lung cancer, learning about immunotherapy for non-small lung cancer patients can help you improve your chances of survival.

Immunotherapy for Non-Small Cell Lung Cancer

While the non-small cell lung cancer diagnostic and treatment landscape is constantly evolving and clinical studies are currently underway to find better ways to eradicate the disease, the increase in survival rates is quite encouraging. In fact, the current survival rates had leaped from only 5 percent to 15.5 or 23.2 percent (depending on if treatment is naïve or not) for this type of cancer before immunotherapy came into play. Dr. Missak Haigentz is the Professor of Medicine, Rutgers Robert Wood Johnson Medical School and Clinical Director of Oncology Integration, RWJBarnabas Health. Dr. Haigentz claims the rates for survival have shown a whopping four-fold improvement.

Keytruda® is a type of immunotherapy drug called a checkpoint inhibitor, which works by blocking the pathways that can shut down key proteins on the body's immune cells, which play an essential role in allowing cancer cells to grow and spread. These checkpoint proteins include PD-1, PD-L1, and CTLA-4. In the case of Keytruda®, the drug is blocking PD-1. The checkpoint proteins, like PD-1, serve as an indication that your cancer cells or tumor are preventing the immune system from attacking them. As a result, the immune system of the body ignores the tumor, and it will continue to grow. These signals need to be blocked to enable the immune system to see, attack, or eliminate cancerous tumor cells.

"KEYNOTE-001" is the clinical trial that helped generate such results. Merck, one of the popular pharmaceutical companies, funded the trial, which enrolled more than 500 people with advanced non-small cell lung cancer that possessed elevated percentages of key proteins like PD-L1. Note that the patients with the highest protein levels (over 50 percent) had a better overall 5-year survival rate (35.4 percent for treatment-naïve patients). Keytruda® was tested in many types of cancers as well, such as myeloma. Interestingly enough, immunotherapy drugs like Keytruda® are helping people with difficult-to-treat cancers live longer livesand the number of patients eligible for the treatment is growing, too.

When immunotherapy was first introduced, only patients with very specific types of cancer were eligible for immunotherapy. Now, an overall total of 43 percent of all patients with cancer are eligible for at least one of the six checkpoint inhibitor immunotherapy drugs on the market, which include Keytruda® (pembrolizumab), atelizumab, avelumab, ipilimumab, nivolumab, and durvalumab. Of course, it is important to remember that all cancers are different, and with immunotherapy, in particular, being eligible does not necessarily mean your cancer will have a response to the drug. Today, 12.46 percent of patients respond to immunotherapy drugs. It is a big improvement from the one percent of patients who responded to the drugs back in 2011just as a 23.2 percent five-year overall survival rate for non-small cell lung cancer is a big improvement from the five percent rate from pre-immunotherapy days. And the encouraging results suggest the trends will continue.

"These results also tell me that we need something else for the other 70 to 80 percent of patients who are not benefitting," Dr. Herbst said. "We need combinations. We need further research." That further research, Dr. Herbst said, will include personalizing immunotherapy treatment to understand patients' unique sensitivities and resistance to these drugs. "I will tell you we've spent years personalizing targeted therapy, and we still have a lot of work to do," he said, "Now we have to personalize immunotherapy and figure out why some patients respond, and some don't, and what are the different combinations of drugs that we can use."

Does Immunotherapy Have Side Effects?

The risk of side effects, in some aspects, is inevitable with any medical treatment or procedure. Once your immune system starts working at full throttle, it may lead to some serious side effects. It can attack other organs, including the liver, lungs, intestine, and hormone-producing glands. If this occurs, it is important to consult with your healthcare team, and it may warrant ceasing treatment for some time. Many oncologists take patients off their immunotherapy medication to subside the effects. In some instances high dose steroids may be used to improve side effects. Unfortunately, several of the side effects from immunotherapy are irreversible and patients will live with them for long periods of time. "You do not know who it will affect and who it will not. When I start someone on immunotherapy, I say, 'Anything weird, I need to know about it.'" – says Dr. Mohana Roy, Clinical Assistant Professor at Stanford University School of Medicine.

Is Immunotherapy the Right Treatment for Your Non-Small Cell Lung Cancer?

As mentioned above, immunotherapy is a unique treatment that has shown positive results for the indication of non-small cell lung cancer. Practitioners have been using immunotherapy drugs for some time to 'boost' the immune system to recognize and ultimately destroy cancerous cells. However, research on immunotherapies is continuously ongoing. Researchers and scientists are always looking for effective combinations that can help treat malignant tumors. Current immunotherapy options, like Keytruda®, have shown positive evidence in survival rate for both treatment naïve and treatment tolerant patients.

Immunotherapy as the First-Line of Treatment

Immunotherapy is best suited as a first-line treatment option for those whose cancer possesses high levels of checkpoint proteins, like PD-1/PD-L1. Tumors with elevated checkpoint protein levels respond better to drugs like certain checkpoint protein inhibitors compared to other traditionally used treatments. About 70 percent of patients with advanced/late-stage non-small lung cancer have higher levels of protein PD-L1. So, if you have advanced stage metastatic lung cancer with a higher percentage of PD-L1 in cancer cells, your oncologist may prescribe Keytruda® (pembrolizumab) as a first-line treatment option.

Immunotherapy as the Second-Line of Treatment

In some cases, advanced-stage non-small lung cancer may not respond well to traditional platinum-based chemotherapies. This type of cancer can often progress after drug treatment and chemotherapy. Modern checkpoint inhibitors have paved the way as a superior treatment for those who have elevated checkpoint protein expression and have failed traditional therapies, like chemo.

Medications like Imfinzi® (durvalumab) and Keytruda® (pembrolizumab) have been shown to be effective secondary treatment options when other treatments have failed to halt disease progression. Regardless of the specific type of immunotherapy intervention, a therapeutic improvement is typically seen when the patient's cancer possesses elevated key protein expression.

There is the potential for side effects to occur.

"Side effects of immunotherapy, called immune related adverse events, often mimic autoimmune conditions. These are medicated by inflammation of different areas of the body.  The colon, thyroid, lungs, and skin are commonly affected," said Dr. Salman Punekar, an oncologist at NYU Langone, tells SurivorNet.

Other Treatment Options than Immunotherapy

Cancer Vaccines

Researchers are currently working on vaccines that have the potential to help the immune system identify and fight certain cancer types. There are vaccines currently available on the market that help in the prevention of certain cancers, like cervical, vaginal, vulvar, and anal, caused by HPV. Currently, there is no FDA-approved vaccine on the market with the indication of treating non-small cell lung cancer. The following are vaccines that are in the research phase for small cell lung cancer:

• P10s-PADRE
• CIMAvax
• PF-06936308
• T-C902 and GRT-C903
• GRT-C901, GR
• GEN-009

Adoptive Cell Therapy

Adoptive cell therapy is a form of immunotherapy used in the treatment of non-small cell lung cancer. This type of therapy has shown promising results against some cancer types, such as lymphoma and leukemia. In adoptive cell therapy, T-cells are taken out of the body and cloned in large numbers in the laboratory setting. They are then put back inside the body to improve the defense mechanism against cancerous cells. Other forms of this therapy include taking ordinary T-cells and adding a mixture of antibodies and receptors of T-cells to target the specific cancerous tumor cells.

Who Should Not Get Immunotherapy

In general, cancer treatments that can strengthen antitumor immune responses are often synergistic with radiation and chemotherapy. However, as said earlier, immunotherapy does not work for all cancer patients. To determine whether a patient will benefit from innovative immunotherapy, it is crucial to identify specific  biomarkers and ensure your type of cancer will effectively respond to available treatment options. If you have been diagnosed with non-small cell lung cancer and also have certain conditions like autoimmune disease, consider discussing it with your doctor at length before you opt for immunotherapy. Immunotherapy for non-small cell lung cancer is safe for patients with health conditions like rheumatoid arthritis, thyroiditis, lupus, and Crohn's disease. Furthermore, it would be beneficial for your healthcare team to ensure that any chronic and active infection is managed or treated accordingly before undergoing any type of immunotherapy. One's immune system must be healthy and not trying to fight an infection or other disease, so it can focus all of its efforts on identifying and eliminating unwanted cancer cells.

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