Lung cancer - the role of immuno-oncology and the importance of pembrolizumab in its therapy

Abstract

Lung cancer is statistically the most common disorder both in Poland and in the world. It has poor prognosis and a high degree of mortality. According to WHO, it is the sixth cause of deaths among all diseases and the first one in cancer-related deaths. At the onset of the 21st century the molecular biology began exploring more closely metabolic pathways of a tumor and specific genetic mutations were recognized. This has led to the introduction of new molecules after many years of using standard chemotherapy. The first breaking point was development of tyrosine kinase inhibitors for patients with detected EGFR, EML4-ALK or ROS1 mutations. Another important group was immune checkpoint inhibitors, which pembrolizumab is one of representatives. It is a monoclonal antibody that blocks the PD-1/PD-L1 pathway. Under physiological conditions PD-1 plays an important role in regulating cytotoxic T cells activity. It is responsible for their activation, proliferation and secretion. The PD-1/PD-L1 interaction subsides immune responses and promotes self‐tolerance through suppressing T cells activity. It is considered to be a protection against autoimmune response. Studies on the tumor microenvironment have shown that tumor cells are able to use the above described mechanism to escape from the host immune surveillance by expressing PD‐L1, which negatively regulates immune responses by interacting with PD‐1 receptor on T cells. These reports prompted scientists to create monoclonal antibodies that block the PD-1/PD-L1 axis leading to the approval of several drugs that have proven effective in treating a wide variety of cancers, including non-small cell lung cancer (NSCLC). Pembrolizumab gained first FDA approval in 2016. Initially it covered second-line monotherapy treatment of PD-L1 positive advanced NSCLC. However, the approval has been quickly broadened to include patients with PD-L1 expression ≥50% in the first-line setting. Many outcomes of randomized controlled trials regarding the use of pembrolizumab yielded an expansion of its registration in almost every histological subtype of NSCLC. Immunotherapy with pembrolizumab shows a reasonable safety and tolerability profile. The most serious side effects include thyroid dysfunction, autoimmune pneumonia and skin problems. The more common side effects such as fatigue, nausea and diarrhea are mild and usually do not contribute to discontinuation of treatment.

Keywords

• non-small cell lung cancer
• cancer immunotherapy
• pembrolizumab
• programmed cell death receptor 1(pd-1)