Purpose: Real-world data from patients with BRAF^V600-mutated, resected, stage III melanoma treated with dabrafenib plus trametinib as adjuvant targeted therapy are limited, and it is important to gain an understanding of the characteristics of this patient population, as well as of the patient journey. Here we aimed to describe the characteristics, dosage reductions and discontinuations in patients with BRAF^V600E/K-mutated melanoma receiving adjuvant dabrafenib plus trametinib after surgical resection through an Italian managed access program (MAP).
Patients and Methods: Eligible patients had completely resected cutaneous melanoma with confirmed BRAF V600E or V600K mutation, or initially resectable lymph node recurrence after a diagnosis of stage I or II melanoma. The starting dose of dabrafenib and trametinib was 150 mg twice daily and 2 mg once daily, respectively.
Results: A total of 557 patients received dabrafenib plus trametinib through the MAP (stage III resected disease at inclusion, 554). Median age was 54.0 years, and 40.2% of patients were female. The proportion of all treated patients who required a dose reduction was low (10.8%) as was the proportion of patients who discontinued treatment (13.5%). The main reason for treatment discontinuation was adverse events (36.0%).
Conclusion: New treatments, including BRAF-targeted therapies and immunotherapy, have transformed the natural history of melanoma. This is the largest study to date describing patients treated with dabrafenib plus trametinib in routine clinical practice in Italy between 2018 and 2019. Results highlight the characteristics of the patients treated and their journey, as well as the tolerable safety profile of dabrafenib plus trametinib in a real-world patient population.

Keywords: BRAF mutation, dabrafenib, melanoma, real-world, trametinib, managed access program


中文翻译：

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通过意大利管理访问计划在手术切除后接受达拉非尼加曲美替尼辅助治疗的高风险 BRAFV600E/K 突变黑色素瘤的真实世界患者的特征

目的：来自接受达拉非尼加曲美替尼作为辅助靶向治疗的BRAF ^V600突变、已切除的 III 期黑色素瘤患者的真实世界数据有限，了解该患者群体的特征以及患者旅程的一部分。在这里，我们的目的是描述通过意大利管理访问计划（MAP）进行手术切除后接受辅助达拉非尼加曲美替尼治疗的BRAF ^{V600E/K突变黑色素瘤患者的特征、剂量减少和停药。}
患者和方法：符合条件的患者已完全切除皮肤黑色素瘤，并确认有BRAF V600E 或 V600K 突变，或诊断为 I 期或 II 期黑色素瘤后最初可切除的淋巴结复发。达拉非尼和曲美替尼的起始剂量分别为 150 mg 每日两次和 2 mg 每日一次。
结果：共有 557 名患者通过 MAP 接受达拉非尼加曲美替尼治疗（纳入时已切除 III 期疾病，554 名）。中位年龄为 54.0 岁，40.2% 的患者为女性。所有接受治疗的患者中需要减少剂量的比例较低（10.8%），停止治疗的患者比例也较低（13.5%）。停止治疗的主要原因是不良事件（36.0%）。
结论：新疗法，包括 BRAF 靶向疗法和免疫疗法，已经改变了黑色素瘤的自然史。这是迄今为止规模最大的研究，描述了 2018 年至 2019 年意大利在常规临床实践中接受达拉非尼加曲美替尼治疗的患者。结果突出了接受治疗的患者的特征及其旅程，以及达拉非尼加曲美替尼在治疗中的可耐受安全性。现实世界的患者群体。

关键词： BRAF突变、达拉非尼、黑色素瘤、现实世界、曲美替尼、管理访问计划