The most promising in the treatment of many advanced cancers seem to be the so-called immunotherapeutic drugs – experts argued during the 51st Congress of the American Society of Clinical Oncology (ASCO), which was recently held in Chicago.
There were the most scientific reports on immunotherapy. It is primarily about the so-called PD-1 / PD-L-1 inhibitors, i.e. drugs that activate the patient’s immune system to fight cancer cells. This mechanism of the therapy’s action was underestimated for many years, and now it is a significant innovation in oncology – told PAP Prof. Lucjan Wyrwicz from the M. Skłodowska-Curie Oncology Center-Institute in Warsaw.
PD-1 is the so-called negative regulatory receptors on the surface of T-type immune cells, which are produced in the red bone marrow and mature mainly in the thymus, from where they migrate to the peripheral blood and lymphatic organs. When these receptors are triggered, lymphocytes stop being activated by other molecular signals.
PD-1 receptors can also be stimulated by the so-called PD-L-1 or PD-L-2 ligands. They are used by the body to avoid an excessive immune response that is harmful to it, for example during a prolonged viral infection. Thanks to this, it can prevent the so-called immune autoimmunity causing the destruction of one’s own tissues.
Ligands of this type are insidiously used by various types of cancer cells to activate the PD-1 receptor and block the T-lymphocytes directed against them. Thus, the cancer is no longer visible to the immune system and it can develop – explained Prof. Exercise.
Some immunotherapeutic drugs work by disrupting this negative signaling pathway. They block the PD-1 receptor or PD-L-1 ligands so that they cannot bind to it and block T-lymphocytes. As a result, the patient’s immune system better recognizes cancer cells and destroys them more effectively.
Two drugs that work in this way have already been registered in the United States and the European Union. One of them is pembrolizumab, which has been used in the treatment of melanoma since autumn 2014. At the end of last year, nivolumab was registered in the same indication.
Both drugs are also tested in other types of cancer and are gaining new applications. Since March 2015, nivolumab has been approved in the treatment of the so-called squamous cell carcinoma of the wage. Registration of pembrolizumab in the treatment of non-small cell lung cancer is expected soon in the European Union.
Other PD-1 / PD-L-1 inhibitors are also tested. One of them is avelumab, tested in 30 countries around the world on 840 patients suffering from various types of malignant neoplasms. The most advanced trials of this preparation are in the treatment of non-small cell lung cancer. They are in the third, pre-registration phase of research.
Avelumab is being tested in the second phase of clinical trials in the treatment of high-grade neuroendocrine skin cancer originating from the so-called Merkel cells. The drug is also investigated in the treatment of melanoma, breast cancer, ovarian cancer, stomach cancer, as well as bladder and pleural mesothelioma.
Our experience with this type of treatment so far relates to the clinical trial phase, although at the early stage of the research we see very favorable results of this therapy – emphasized prof. Exercise. According to the specialist, an additional advantage of immunotherapy is that it does not cause side effects typical for traditional chemotherapy, such as nausea, vomiting, alopecia and increasing fatigue.
However, it is not a treatment completely devoid of side effects. Those that target the PD-L1 mechanism can induce a response of the immune system to the patient’s normal organs, such as the liver and intestines. These are rare complications, although they mean that treatment of this type should be carried out in reference centers – adds the specialist.
Unfortunately, at this stage we do not have easy access to avelumab for our patients – added prof. Exercise. – A chance for them are clinical trials conducted in Poland with this drug in a wide group of cancers, incl. in patients with gastric cancer, melanoma, head and neck tumors or urological neoplasms.