Gebhardt Christoffer, Debus Dirk, Rohrer Peter, Kähler Katharina C, Koch Lukas, Terheyden Patrick, Nguyen Van Anh
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Department of Dermatology, University Hospital of the Paracelsus Medical Private University, Nürnberg, Germany.
Melanoma Manag. 2025 Dec;12(1):2545167. doi: 10.1080/20450885.2025.2545167. Epub 2025 Aug 28.
The management of advanced, unresectable, or metastatic BRAFV600-mutated melanoma is complex, particularly regarding therapy sequencing with targeted therapies (TT) and immune checkpoint inhibitors (ICI). The REMINISCENCE project aimed to enhance individualized therapy approaches by analyzing case reports of patients undergoing encorafenib and binimetinib (EB) therapy. This report discusses three melanoma patients with brain metastases treated in Germany and Austria, emphasizing personalized treatment strategies in BRAFV600-mutated melanoma, particularly when both ICI and TT are available. The timing for transitioning between therapies remains contentious, with many patients experiencing disease progression during or after adjuvant therapy. Findings from clinical trials like DREAMseq, SECOMBIT, EBIN, and ImmunoCobiVem may not directly apply to this evolving clinical landscape due to the impact of prior therapies on the tumor microenvironment. The variations in trial designs further complicate sequencing strategies. Emerging methods, such as early circulating tumor DNA (ctDNA)-guided approaches, present potential pathways for personalized treatment. Ongoing research into sequencing therapy is crucial for improving clinical outcomes. To determine the most effective treatment sequences based on individual medical histories, genetic profiles, and treatment goals, there is an urgent need for prospective biomarker-driven clinical trials.
晚期、不可切除或转移性BRAFV600突变黑色素瘤的管理很复杂，尤其是在靶向治疗（TT）和免疫检查点抑制剂（ICI）的治疗顺序方面。REMINISCENCE项目旨在通过分析接受恩考芬尼和比美替尼（EB）治疗的患者的病例报告来加强个体化治疗方法。本报告讨论了在德国和奥地利接受治疗的三名患有脑转移的黑色素瘤患者，强调了BRAFV600突变黑色素瘤的个性化治疗策略，特别是当ICI和TT都可用时。治疗之间转换的时机仍然存在争议，许多患者在辅助治疗期间或之后经历疾病进展。由于先前治疗对肿瘤微环境的影响，DREAMseq、SECOMBIT、EBIN和ImmunoCobiVem等临床试验的结果可能无法直接应用于这种不断演变的临床情况。试验设计的差异进一步使测序策略复杂化。新兴方法，如早期循环肿瘤DNA（ctDNA）引导的方法，为个性化治疗提供了潜在途径。持续开展测序治疗研究对于改善临床结果至关重要。为了根据个体病史、基因谱和治疗目标确定最有效的治疗顺序，迫切需要开展前瞻性生物标志物驱动型临床试验。
