Jakub Jarosz, Anna Wesołowska, Paweł Różanowski

Lung cancer – the role of immunooncology and the importance of pembrolizumab in its therapy
2023-05-05

Lung cancer is statistically the most common disorder both in Poland and in the world. It has a poor prognosis and a high degree of mortality. According to WHO, it is the sixth cause of death among all diseases and the first one in cancer-related deaths.

At the onset of the 21st century molecular biology began exploring more closely the metabolic pathways of tumors 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 the development of tyrosine kinase inhibitors for patients with detected EGFR, EML4-ALK, or ROS1 mutations. Another important group was immune checkpoint inhibitors, of which pembrolizumab is one of the 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 by 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 receptors 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 its 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: cancer immunotherapy, non-small cell lung cancer, pembrolizumab, programmed cell death receptor 1(PD-1).

© Farm Pol, 2022, 78(12): 717–733