Abstract
Therapeutic options for treating advanced melanoma are progressing rapidly. Until six years ago, the regimen for treating advanced melanoma mainly comprised cytotoxic agents such as dacarbazine, and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have become recognized as anchor drugs for treating advanced melanoma with or without additional combination drugs such as ipilimumab. In addition, v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase inhibitors in combination with mitogen-activated protein kinase kinase (MEK) inhibitors are among the most promising chemotherapeutic regimens for treating advanced BRAF-mutant melanoma, especially in patients with low tumor burden. Since anti-PD1 antibodies are widely applicable for the treatment of both BRAF wild-type and mutated advanced melanomas, several clinical trials for drugs in combination with anti-PD1 antibodies are ongoing. This review focuses on the development of the anti-melanoma therapies available today, and discusses the clinical trials of novel regimens for the treatment of advanced melanoma.
Highlights
Until 2014, regimens for the treatment of advanced melanoma mainly comprised cytotoxic agents such as dacarbazine (DTIC) and cytokines (e.g., type I interferon (IFN), high-dose interleukin (IL)-2, etc.) [1,2,3,4,5,6]
Since anti-programmed cell death 1 (PD1) Abs are widely applicable to the treatment of both BRAF wild-type and mutated advanced melanoma, several clinical trials for drugs combined with anti-PD1 Abs are ongoing—see Section 5
The additional benefit of DTIC was evaluated, but no significant effect of additional IFN-α on overall survival was seen for advanced melanoma patients [1]
Summary
Until 2014, regimens for the treatment of advanced melanoma mainly comprised cytotoxic agents such as dacarbazine (DTIC) and cytokines (e.g., type I interferon (IFN), high-dose interleukin (IL)-2, etc.) [1,2,3,4,5,6]. Amagai et al reported a case series with pyrexia developing from advanced melanoma treated with E + B therapy, and suggested that serum levels of soluble CD163 as well as IFN-γ induced chemokines [C-X-C motif chemokine (CXCL9, CXCL10, CXCL11)] were increased in the pyrexia group compared with the non-pyrexia group [42] All of these soluble factors had previously been reported as biomarkers for adult-onset Still’s disease (AOSD) [44,45], and the manifestations of AOSD (including pyrexia, transient skin rash, fatigue and arthritis [44,45]) are well-known AEs developing from BRAF/MEK inhibitors [40]. Nivolumab followed by D + T combination therapy can cause severe drug eruption such as exudative erythema multiforme [49] Those reports suggest that the subsets and incident ratio of severe adverse events (SAEs) caused by BRAF/MEK inhibitors might differ from those in previously published clinical studies in the real world
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