Abstract
There are now multiple effective, well-tolerated, FDA-approved systemic therapy options for the treatment of advanced melanoma, as well as exciting new immunotherapy and targeted therapy agents currently in clinical trials. Both traditional cytotoxic chemotherapy and targeted BRAF inhibitors can increase antigen presentation and can rebalance the intratumoral immune milieu. The combination of pulsed cytotoxic therapy and immunotherapy is a logical next step forward in designing treatment regimens. Combination radiotherapy and immunotherapy also has experimental and clinical support. Not all combinations are likely to be additive or synergistic; indeed in some murine models, BRAF inhibitors may be more cytostatic than cytotoxic in tumors with PTEN loss, and may actually deter immune response. Additionally, combinations of drugs with apparently nonoverlapping toxicities can lead to unexpected adverse events, as has been shown in ipilimumab (Yervoy) + vemurafenib (Zelboraf). The standard of care for patients with advanced melanoma remains participation in clinical trials in order to enhance our understanding of the effectiveness and toxicities of combination regimens, and there remains a need for correlative studies (e.g., serial biopsies) to further elucidate the alterations in the tumor microenvironment engendered by combination therapy and allow for customization of regimens to tumor genotype.
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Abri, K., Daud, A.I. (2018). Combinatorial Approach to Treatment of Melanoma. In: Fisher, D., Bastian, B. (eds) Melanoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7322-0_18-1
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