Jia Dong-Dong, Xu Yu, Ren Zhi-Wu, Li Lin-Qing, Zhang Lei, Li Yang, Lou Li-Shu, Yao Wei-Tao, Liu Zhe, Li Xian-An, Yang Ji-Long, Chen Yong, Li Tao
Department of Bone and Soft-Tissue Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, Hangzhou, China.
Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
J Dermatol. 2025 Jul;52(7):1146-1151. doi: 10.1111/1346-8138.17779. Epub 2025 May 14.
Pathogenic BRAF mutations drive constitutive MAPK pathway activation in melanoma, and targeted therapies with dabrafenib plus trametinib have improved outcomes in the adjuvant setting. However, the optimal duration of adjuvant therapy remains unclear. This retrospective study examined whether extending dabrafenib plus trametinib beyond 1 year offers additional clinical benefit in Chinese patients with resected Stage III melanoma.
Medical records from six centers were reviewed for adults with BRAF V600E/K-positive, completely resected Stage III melanoma who received at least 12 months of adjuvant dabrafenib plus trametinib. Patients were divided into a 1-year therapy group and a more-than-1-year therapy group. Relapse-free survival (RFS) was the primary end point; adverse events were also assessed.
Of the 122 patients included, 77 received more than 1 year of adjuvant therapy. The more-than-1-year group experienced significantly better RFS (log-rank p = 0.04), and longer therapy independently reduced recurrence risk in multivariate analysis (HR, 2.42; p = 0.035). Adverse event profiles did not differ between groups, and toxicity-related treatment modifications occurred primarily within the first year.
Extending dabrafenib plus trametinib beyond 1 year may provide improved RFS without increasing toxicity. Further prospective trials are warranted to confirm the impact on overall survival and identify optimal patient subsets for prolonged therapy.
致病性BRAF突变驱动黑色素瘤中丝裂原活化蛋白激酶（MAPK）通路的组成性激活，在辅助治疗中，达拉非尼联合曲美替尼的靶向治疗改善了治疗效果。然而，辅助治疗的最佳持续时间仍不明确。这项回顾性研究探讨了在中国切除的III期黑色素瘤患者中，将达拉非尼联合曲美替尼的治疗时间延长至1年以上是否能带来额外的临床益处。
回顾了六个中心的医疗记录，纳入BRAF V600E/K阳性、完全切除的III期黑色素瘤成年患者，这些患者接受了至少12个月的辅助达拉非尼联合曲美替尼治疗。患者被分为1年治疗组和超过1年治疗组。无复发生存期（RFS）是主要终点；同时也评估了不良事件。
在纳入的122例患者中，77例接受了超过1年的辅助治疗。超过1年治疗组的RFS显著更好（对数秩检验p = 0.04），在多变量分析中，更长时间的治疗独立降低了复发风险（风险比，2.42；p = 0.035）。两组之间的不良事件谱没有差异，与毒性相关的治疗调整主要发生在第一年。
将达拉非尼联合曲美替尼的治疗时间延长至1年以上可能在不增加毒性的情况下改善RFS。有必要进行进一步的前瞻性试验，以确认对总生存期的影响，并确定适合延长治疗的最佳患者亚组。
