Lung cancer is the leading cause of cancer-related deaths in the United States. According to the American Cancer Society, approximately 224,390 people will be diagnosed with lung cancer in 2016, and more than 158,000 patients will die from this disease. Smoking is the major risk factor for lung cancer–80% of lung cancer deaths are related to smoking.
Genetics play a role in families with a history of lung cancer, especially those with certain genetic mutations (alteration), such as ALK or EGFR mutations, which increase the risk for lung cancer.
Non–small-cell lung cancer (NSCLC) is the most common type of lung cancer. Treatment for NSCLC may include chemotherapy, radiation therapy, radiofrequency ablation, surgery, targeted treatment, and, most recently, immunotherapy. Immunotherapy uses the body’s own immune system to help fight the cancer.
Our immune system helps to protect the body from infections and diseases. The immune system keeps track of all substances that are normally found in our body, and attacks substances that are perceived as foreign, such as germs or cancer cells. However, sometimes the immune system does not recognize cancer cells as foreign entities, allowing those cells to grow instead of stopping them from becoming a tumor.
Immunotherapy
Immunotherapy enhances the body’s immune system and is therefore an effective strategy for some cancers, including NSCLC. This enhancement of the immune system can be accomplished (1) by stimulating the immune system to attack cancer cells, or (2) by giving the immune system man-made immune system proteins.
Some immunotherapies may boost the body’s overall immune system, and others help train the immune system to attack cancer cells specifically.
Immune Checkpoint Inhibitors Approved for Lung Cancer
The main types of immunotherapies for cancer include “monoclonal antibodies,” “immune checkpoint inhibitors,” cancer vaccines, and nonspecific immunotherapies.
Immune checkpoints are molecules that are located on certain immune cells, such as T-cells. These checkpoints allow the immune system to distinguish between normal cells and foreign cells, such as cancer cells. Cancer cells sometimes use immune checkpoints to avoid being attacked. However, immune checkpoint inhibitor drugs are being developed to target immune checkpoints by strengthening the body’s immune system to fight cancer cells so that the immune system can continue to destroy cancer cells.
In late 2015, the FDA approved 2 immune checkpoint inhibitors for the treatment of patients with advanced NSCLC–Keytruda (pembrolizumab) and Opdivo (nivolumab). These drugs block PD-1 or PD-L1, a type of protein on the immune system and on some cancer cells. By blocking the PD-1 or PD-L1 pathway, Keytruda and Opdivo boost the body’s immune response against cancer cells, which helps the immune system to shrink the tumor or to slow its growth.
Keytruda is approved for patients with NSCLC that is unresectable (cannot be removed by surgery) or metastatic (has spread to other organs), and for patients with NSCLC and the ALK mutation. It is intended to be used after a special test to identify patients with PD-L1 expression who are most likely to benefit from this type of therapy.
Opdivo is approved for patients with metastatic NSCLC, and can also be used after the test for PD-L1 expression, although this test is not required for using Opdivo.
In addition, although not an immunotherapy, another new medication–the tyrosine kinase inhibitor Alecensa [alectinib]–was approved by the FDA in late 2015 specifically for patients with NSCLC and the ALK mutation.
New Immunotherapies in Development
Several immune checkpoint inhibitors are being studied in clinical trials for lung cancer. Several PD-L1 inhibitors are currently in clinical trials for the treatment of patients with NSCLC, including Tecentriq (atezolizumab), which was recently approved by the FDA for bladder cancer, and 2 investigational drugs in clinical trials–durvalumab and avelumab.
CTLA-4 is another molecule on T-cells that may stop the immune system from attacking cancer cells; therefore, drugs that are CTLA-4 inhibitors may be able to block that molecule and improve the immune system’s ability to fight the cancer.
Yervoy (ipilimumab), which is currently approved by the FDA for melanoma, and the investigational drug tremelimumab, are CTLA-4 inhibitors that are being studied in clinical trials for the treatment of patients with NSCLC. Several of the immune checkpoint inhibitors that are FDA approved and in clinical trials are listed in the Table.
Vaccines for Lung Cancer
Vaccines are a new way to treat some types of cancer. Currently, no vaccine has been approved by the FDA for lung cancer, but several types of vaccines that may be able to boost the body’s immune response against lung cancer cells are being investigated in clinical trials, such as the TG4010 vaccine; these vaccines are intended to treat rather than prevent lung cancer.
