Can immunotherapy be a new game-changer in our fight against lung cancer?
Dr. Brendon Stiles, chief of thoracic surgery and surgical oncology at Montefiore Health System (previously a thoracic surgeon at Weill Cornell Medical Center), tells SurvivorNet that there’s a huge amount of promise. "Immunotherapy is here to stay. And it’s really changed the face of lung cancer, just like targeted therapies,” Dr. Stiles explains.Read More
What is immunotherapy for cancer?Immunotherapy is a type of biological therapy that ushers the power of a person's immune system to recognize and conquer cancer cells. This includes recruiting internal mechanisms like the body's proteins, white blood cells, tissues, and organs or through external mechanisms by synthesizing molecules in the lab.
Each type of immunotherapy works differently depending on many factors. While some will work to kill or destroy cancer cells, others will only stop them from growing and spreading to other organs. According to Johns Hopkins Medicine, the overall response to immunotherapy ranges between 15-20%.
Immunotherapy treatment has shown success in many types of cancers leading to longer survival rates and long-lasting remissions, so much so that it's an especially exciting area of development when it comes to treating lung cancer.
"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.
What are the different types of lung cancer immunotherapy? And how do they work?
So far, immune checkpoint inhibitors are considered the only type of immunotherapy for lung cancers that have been approved by the FDA, with real-world evidence of their efficacy.
Our immune system is generally programmed to distinguish between normal cells and foreign cells (these can be from infection by bacteria or viruses or by uncontrolled growth of a cell turning into a cancer cell). Immune checkpoints play a critical role in regulating this mechanism.
To do this, the immune system labels normal cells with these 'protein molecules' known as immune checkpoints that act as switches to inhibit an immune response against a cell. However, cancer cells sometimes trick the immune system by displaying these molecules on their surface to avoid getting recognized as foreign cells and destroyed.
There have been successful Immunotherapy drugs that prevent the immune system from getting tricked by cancer cells through immune checkpoint inhibitors. For lung cancer, one such example is blocking the 'PDL1-PD1' interaction. Similarly, this also works for blocking the 'CTLA4' immune checkpoint, where the immune system can recognize the cancer cell and stimulate an immune response.
What are the available immunotherapy drugs for cancer?
Not long ago, the FDA successfully approved several immune checkpoint inhibitors for Non-Small Cell Lung Cancer (NSCLC) that have shown great results. Some of these immunotherapy agents have also been approved for the treatment of Small Cell Lung Cancer (SCLC) These immunotherapy drugs include the following:
- Pembrolizumab (Keytruda) and Nivolumab (Opdivo). These target PD-1 protein which is found on T-cells (immune system cells).
- Durvalumab (Imfinzi) and Atezolizumab (Tecentriq). These target PDL-1 protein which is found on cancer cells.
- Ipilimumab (Yervoy). This targets CTLA-4 protein and should be used in combination with another therapy.
These drugs are given intravenously to block the interaction between protein checkpoints that helps in identifying and eliciting a strong immune reaction against cancer cells to slow their growth and reduce their size.
The decision of which type of drug to take or whether it should be taken alone or combined with other medication is made depending on the cancer stage and the patient's case. However, it's imminent to test for the presence of these proteins first before initiating treatment.
Side effects of immunotherapy for lung cancer
The safety of immunotherapy for lung cancer can vary according to each patient. The most common side effects encountered resemble flu-like symptoms, these are:
- Shortness of breath
- Loss of appetite
- Muscle and bone pain
As for the more serious but less occurring side effects, these usually involve:
- 'Autoimmune reaction' where the body can mistakenly attack normal cells of other organs like the liver, kidney, etc., which can pose a higher threat of organ damage if not managed. Some of this toxicity may be irreversible and long lasting.
- 'Infusion reaction' this happens during the administration of the drug and resembles signs of an allergic reaction like swelling, inflammation, itchiness, wheezing, or dizziness.
If any of these serious side effects develop, it's very important to seek medical assistance to stop the treatment immediately and start taking medication to suppress the immune system.
How successful is immunotherapy for lung cancer?
Despite being a relatively new treatment option for lung cancer, immunotherapy has changed the meaning of lung cancer by rewriting the projected life expectancy of its patients. This was evident in a study conducted in 2018 on 21 Non-Small Cell Lung Cancer (NSCLS) patients who were scheduled to undergo surgery. The results revealed that after 2-4 weeks of treatment, 45% of the patients had fewer cancer cells with minor side effects.
Another study that was done on the checkpoint inhibitor drug Pembrolizumab, showed that it had a significant anticancer effect, considerable safety, and provided enhanced long-term effect for patients with advanced NSCLC.
How is immunotherapy different from other lung cancer treatments?
Immunotherapy differs from other conventional therapies through its mode of action. Additionally, in certain circumstances, they may be a better choice than other traditional treatments like surgery, chemotherapy, or radiotherapy, depending on each patient’s unique circumstances.
What's next in immunotherapy for lung cancer?
With decades' worth of research into how lung cancer works, and immunotherapeutic agents being tested in clinical trials, there are a lot of promising new candidates that open the door for patients to a much better survival chance than ever was. So far, the focus is on the following:
Chimeric Antigen T-Cell Receptor (CAR-T)
Although not yet approved by the FDA for lung cancer treatment, this one shows great promise in coaxing the immune system to target cancer cells and destroy them with very high efficacy. CAR-T cell therapy is done by removing some T-cells a type of immune cell responsible for fighting off cancer from the patient's body, modifying them in the lab, and re-inserting it back to specifically target cancer cells.
Currently, CAR-T cell immunotherapy has only been approved for cancer in the blood (i.e., acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma). As for lung cancer, it's still under study in clinical trials.
Contrary to conventional vaccines, cancer vaccines are considered more of a therapeutic vaccine that boosts the immune system in finding and killing already pre-existing cancer cells as opposed to preventing disease. This works by giving vaccines that contain cancer-specific proteins that are not available or scarcely available on normal cells. The goal is to optimize a vaccine that can target cancer cells only, but, like CAR-T immunotherapy, this treatment is still under investigation and hasn't been approved yet by the FDA.
Combining Immunotherapy with other conventional therapies
There have been increased efforts to determine the efficacy and safety of pairing up immunotherapy with other traditional therapies like chemotherapy and radiotherapy. For instance, a study in 2018 planned on dividing 616 patients to either receive (chemotherapy and immunotherapy) or (chemotherapy and placebo) and measured the outcome after 12 months.
Even though the outcome of this trial proved that those who took immunotherapy showed a higher survival rate of 69.2%, while those who took chemotherapy only showed a lower survival rate of 49.4%; It also revealed that the first group suffered severe side effects. Thus, there's a need to conduct more research on pairing up therapies.
"Historically, early-stage lung cancers have been treated with surgery, plus chemotherapy administered before or after surgery to reduce the risk of recurrence," Dr. Benjamin Herzberg, a medical oncologist specializing in thoracic malignancies at Columbia University's Herbert Irving Comprehensive Cancer Center, previously told SurvivorNet. "Now, with the FDA approval of the immunotherapy drug nivolumabgiven alongside chemotherapy and prior to definitive surgerywe have another option to offer patients to reduce the risk of cancer coming back."
The Bottom Line
Following the words of Dr. Stiles, "What people are most excited about is if you look out over the long-term and at survival, people talk about a plateau â€¦ it's still early, but â€¦ people are at least raising the question: Can we see cures with immunotherapy and lung cancer?"
This is indeed what it's all about, keeping in mind some minor inconveniences that can hold back this technology like its high cost, and the lack of suitability for all patients (Cancer patients who have autoimmune diseases will possibly not be eligible for the treatment).
With time and consistent research to investigate the long-term outcome of immunotherapy for lung cancer, we may have an excellent solution on our hands that can perhaps eliminate many incurable diseases including lung cancer.