Chemotherapy drugs have been used for decades to treat malignancies. They are often effective in killing cancerous cells; however, there is significant collateral damage. They are toxic substances that also weaken or kill other cells in the body. Thus, significant research is focused on alternatives. The most promising area of research is focused on the body’s immune system—stimulating it to recognize and destroy malignant cells without harming other cells. Now, UCLA researchers have found that the immunotherapy drug pembrolizumab (Keytruda) is more effective than chemotherapy for patients with advanced lung cancer. The findings were published online on December 19 in the journal The Lancet.
Worldwide, lung cancer is the leading cause of cancer deaths; the American Lung Association estimates that more than 158,000 individuals in the US will die from the disease this year alone. Non-small cell lung cancer accounts for approximately 85% of all lung cancers.
The study authors note that more than 1,000 individuals with PD-L1 expressing non-small-cell lung cancer were enrolled in their clinical trial, which compared the immunotherapy drug pembrolizumab to the established standard chemotherapy drug docetaxel. The study found that patients receiving the immunotherapy lived longer than those who received chemotherapy, noted senior author Edward Garon, MD, a researcher at the UCLA Jonsson Comprehensive Cancer Center and an associate professor of hematology and oncology at the David Geffen School of Medicine. Dr. Garon explained, “This treatment provides real hope of long-lasting responses while avoiding the toxicities of typical chemotherapy in a broad population of lung cancer patients. “We are excited that these results have identified a larger group of patients for whom in general, immunotherapy is a superior treatment option than our traditional approaches.”
Keytruda is an antibody that targets the protein PD-1, which is expressed by immune cells. When it binds to PD-L1, PD-1 acts as an immune checkpoint, inhibiting the immune system’s T cells that otherwise could attack cancer cells. Some tumors are able to avoid an immune response by expressing PD-L1. Therefore, by blocking the interaction between PD-1 and PD-L1, Keytruda enables the patient’s immune system to attack the cancer.
Because PD-L1 binding to PD-1 prevents the T cells from attacking cells, it had been thought that PD-L1 levels in malignancies could correlate with favorable clinical outcomes with PD-1 inhibitor treatment. This theory was validated in a study led by Garon and published earlier this year in the New England Journal of Medicine.
Approximately two thirds of patients enrolled in the clinical trial whose tumor could be tested were PD-L1-positive (meaning that PD-L1 expressed in at least 1% of their tumor cells). The participants were randomly assigned to different treatment groups; two groups received differing doses of immunotherapy, and a third group receiving the chemotherapy. The investigators found that patients receiving the immunotherapy were more likely to have their tumor shrink significantly––and more importantly––the patients who received the immunotherapy lived significantly longer than those who received chemotherapy. Furthermore, the rate of serious toxicity related to therapy (defined using a common clinical trial criteria), was lower in the patients who received pembrolizumab.
Dr. Garon explained, “By continuing to refine and expand our selection of patients who stand to benefit from this type of therapy, we are profoundly changing the way that patients with this common cancer are treated. For most patients, this now offers data showing that immunotherapy leads to superior clinical outcomes with a side effect profile that is generally favorable to our traditional therapies.”