Systemic Therapy of Metastatic Melanoma: On the Road to Cure

Abstract

This decade has brought significant survival improvement in patients with metastatic melanoma with targeted therapies and immunotherapies. As our understanding of the mechanisms of action of these therapeutics evolves, even more impressive therapeutic success is being achieved through various combination strategies, including combinations of different immunotherapies as well as with other modalities. This review summarizes prospectively and retrospectively generated clinical evidence on modern melanoma therapy, focusing on immunotherapy and targeted therapy with BRAF kinase inhibitors and MEK kinase inhibitors (BRAF/MEK inhibitors), including recent data presented at major conference meetings. The combination of the anti-PD-1 directed monoclonal antibody nivolumab and of the CTLA-4 antagonist ipilimumab achieves unprecedented 5-year overall survival (OS) rates above 50%; however, toxicity is high. For PD-1 monotherapy (nivolumab or pembrolizumab), toxicities are in general well manageable. Today, novel combinations of such immune checkpoint inhibitors (ICIs) are under investigation, for example with cytokines and oncolytic viruses (i.e., pegylated interleukin-2, talimogene laherparepvec). Furthermore, current studies investigate the combined or sequential use of ICIs plus BRAF/MEK inhibitors. Several studies focus particularly on poor prognosis patients, as e.g., on anti-PD-1 refractory melanoma, patients with brain metastases, or uveal melanoma. It is hoped, on the road to cure, that these new approaches further improve long term survival in patients with advanced or metastatic melanoma.

Novel agents in a young patient with osteosarcoma: A short review

“…In addition to TKIs, checkpoint inhibitors (CPI) have gained much attention in the last decade due to their widespread use in various oncologic diseases [22,23]. Therefore, after failure of pazopanib and second pulmonary R0 resection, experimental off-label treatment with pembrolizumab was initiated.…”

Characterization of m6A-Related Genes Landscape in Skin Cutaneous Melanoma to Aid Immunotherapy and Assess Prognosis

“…10 However, adverse drug events are also on the rise, and only a small percentage of people will benefit from these therapies. 11 The treatment of SKCM patients remains an evolving and difficult subject. 12 Therefore, the development of truly meaningful prognostic markers for SKCM patients is of profound importance to assess the clinical outcome and long-term prognosis of patients.…”

The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells

“…These options could increase the overall survival rates, although the development of drug resistance is an emerging issue [ 7 ]. To overcome resistance, targeting multiple cellular pathways with combination treatments may be effective [ 8 ]. Combinations can also result in greater clinical activity compared to the clinical activity of the individual drugs.…”