BACKGROUND Brain metastases (BM) and lactate dehydrogenase (LDH) levels above the upper limit of normal (ULN) are associated with poor prognosis in patients with melanoma. Although treatment with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib have demonstrated long-term clinical benefit in patients with melanoma, data on their efficacy in patients with BM are limited. METHODS DESCRIBE Italy is an observational, retrospective, real-world study evaluating dabrafenib plus trametinib in 499 patients with BRAFV600-mutant stage III unresectable or stage IV melanoma from various sites across Italy. Here, we analyzed the clinical outcomes for the subgroup of patients receiving first-line treatment and presenting with BM at diagnosis and assessed the impact of predictive factors such as LDH levels and the presence of other metastases on median progression-free survival (mPFS). RESULTS Overall, 325 evaluable patients were on first-line therapy and are the focus of this analysis; of these, 76 patients (23.4%) had BM at baseline. mPFS was lower for patients with BM at baseline compared with overall patients (8.7 months vs 9.3 months, respectively). Patients with BM at diagnosis and LDH >ULN had a considerably shorter mPFS compared with patients with LDH ⩽ULN (5.3 months vs 9.9 months, respectively). mPFS was noticeably longer for patients with cerebral metastases only compared with patients with cerebral and other metastases (15.0 months vs 8.7 months, respectively). CONCLUSIONS Dabrafenib plus trametinib showed effectiveness in a real-world population of patients with advanced BRAFV600-mutated melanoma and BM at baseline, supporting its use in this population with poor outcomes.

中文翻译：

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基线时接受达拉非尼加曲美替尼治疗的 BRAFV600 突变黑色素瘤和脑转移患者的结果。

背景脑转移瘤（BM）和乳酸脱氢酶（LDH）水平高于正常上限（ULN）与黑色素瘤患者预后不良相关。尽管 BRAF 抑制剂达拉非尼和 MEK 抑制剂曲美替尼治疗已证明对黑色素瘤患者具有长期临床益处，但其对 BM 患者疗效的数据有限。方法描述意大利是一项观察性、回顾性、真实世界研究，评估了意大利各地 499 名 BRAFV600 突变 III 期不可切除或 IV 期黑色素瘤患者的达拉非尼加曲美替尼治疗。这里，我们分析了接受一线治疗并在诊断时出现 BM 的患者亚组的临床结果，并评估了 LDH 水平和其他转移等预测因素对中位无进展生存期 (mPFS) 的影响。结果 总体而言，325 名可评估患者正在接受一线治疗，也是本次分析的重点；其中，76 名患者 (23.4%) 在基线时有 BM。与总体患者相比，基线时患有 BM 的患者的 mPFS 较低（分别为 8.7 个月和 9.3 个月）。与 LDH ≤ ULN 的患者相比，诊断时患有 BM 且 LDH > ULN 的患者的 mPFS 显着缩短（分别为 5.3 个月和 9.9 个月）。仅脑转移患者的 mPFS 明显长于脑转移和其他转移患者（15.0 个月 vs 8.0 个月）。分别为 7 个月）。结论 达拉非尼联合曲美替尼在基线时患有晚期 BRAFV600 突变黑色素瘤和 BM 的现实世界患者群体中显示出有效性，支持其在这一结果不佳的人群中的使用。