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Introduction: The emergence of molecularly targeted agents and immune checkpoint inhibitors has positively revolutionized the management and prognosis of BRAF-mutant metastatic melanoma. However, the availability of both therapeutic options, with their pros and cons, rationally triggered clinical considerations for the optimum frontline and subsequent treatment decisions.Areas covered: Here, we debate all approved therapies in patients with BRAF-mutant metastatic melanoma evaluating their efficacy and safety based on their pivotal trials. With prospective randomized data pending, retrospective comparisons of BRAF/MEK versus immune checkpoint inhibitors are reviewed to recognize any advantage between these two alternatives and to optimize their implementation. Preclinical and early clinical results of combining concurrently or sequentially targeted therapy and immunotherapy are also discussed.Expert opinion: BRAF/MEK inhibitors produce rapid and deep responses and should be included in first-line approaches, particularly in cases with aggressive and bulky disease, while single or double checkpoint inhibition lead to more durable responses and could be involved either in frontline treatment of BRAF-mutant melanoma with less unfavorable characteristics or in maintenance after initial targeted induction or in future immune/targeted regimens for high-risk groups. Data from ongoing trials directly comparing or combining these strategies are expected to update their role in a more individualized basis. [ABSTRACT FROM AUTHOR]

Purpose: Survivin represents a key anti-apoptotic molecule that is highly expressed in the vast majority of tumors. The aim of the study was to examine the significance of survivin mRNA blood levels in melanoma patients., Methods: In this prospective translational research study, survivin mRNA blood levels were measured in melanoma patients treated with adjuvant interferon or systemic treatment for advanced disease., Results: Sixty-four patients with melanoma and 40 healthy controls were included. The majority of them had tumor stages III and IV. The upper 95% confidence interval (95%CI) of survivin levels in controls was set as normal cut-off. Fifty-two (81.3%) patients had survivin levels above normal cut-off. Melanoma patients had higher survivin levels than controls (p<0.0001). Survivin levels were non-significantly higher in stage III compared to stage IV patients. Patients with survivin levels above vs. below median had median progression-free survival (PFS) 19.5 months vs. 7.4 months (p=0.045), but median overall survival (OS) not reached vs. 18.4 months (p=0.091). Cox proportional hazard models showed that only tumor stage was associated with PFS and OS. There was no statistically significant change in survivin levels between baseline and during treatment (p=0.845) or during follow-up (p=0.101)., Conclusion: Although melanoma patients had significantly higher survivin levels than controls, the study showed that survivin mRNA blood levels did not represent an independent prognostic factor for patients with melanoma. The role of circulating survivin should be further examined in larger studies.