Combined or sequential treatment of advanced melanoma?

Abstract

Melanoma is a malignant neoplasm with a very high rate of growth in the number of cases. In Poland, in the years 1980-2010, the number of cases of melanoma increased threefold. Although the incidence rates of melanoma are rising, the mortality rate due to melanoma is falling. In recent years, the treatment of patients with melanoma has changed to a great extent. Thanks to the development of molecular research, the presence of specific mutations in melanoma cells was discovered. The progress in understanding the molecular mechanisms occurring in this neoplastic cells and the interaction between the immune system cells and melanoma cells contributed to the development of new classes of drugs: immunotherapy and targeted therapy. With the use of checkpoint inhibitors, long-term remission of the disease can be achieved, which has been confirmed in many clinical trials that have shown improvements in overall survival (OS) and progression free survival (PSF). However, the predominant problem is the low response rate to checkpoint inhibitors and the time between the initiation of therapy and the response to treatment. This is not the case with targeted therapies, where the response rate is high and the response time is very short. Therefore, a promising treatment strategy can be a combination of these two classes of drugs, so that one can try to achieve a quick and long-term response to the treatment. The paper discusses the current treatment options for melanoma patients in the spreading phase of the disease and analyzes the benefits of combined and sequential treatment.

Real-world treatment practice in patients with advanced melanoma

“…Immunotherapy uses immune checkpoint inhibitors (ICIs), which include anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibodies – ipilimumab and antibodies against the programmed cell death-1 (anti-PD-1) inhibitors – nivolumab and pembrolizumab [ 13 ]. Targeted therapy includes BRAF proto-oncogene serine/threonine kinase inhibitors (BRAFi; vemurafenib, dabrafenib, and encorafenib) and MEK inhibitors (MEKi; cobimetinib, trametinib, and binimetinib) [ 14 ].…”