背景:BRAFV600突变是黑色素瘤中最常见的致癌变异,在约50%的皮肤和10%-15%的肢端或粘膜亚型中可见。目前,抗PD-1阻断的免疫治疗和Dabrafenib联合曲美替尼(D+T)靶向治疗的双靶向治疗已被批准作为具有BRAFV600突变的III期黑色素瘤的辅助治疗.根据他们的III期临床试验,两种治疗的3年无复发生存率(RFS)约为60%。然而,与免疫治疗相比,靶向治疗的早期疾病控制效果略好.随着中国药品审批期限的不同,抗PD1单药治疗,D+T组合,和Vemurafenib(V)单药治疗近年来都已在实际临床实践中用作III期BRAF-mut黑色素瘤的辅助治疗。我们进行了这项回顾性研究,以评估不同治疗方法在中国黑色素瘤人群中的疗效。
方法:对2017年1月至2021年12月复旦大学附属上海肿瘤中心行根治性手术并经病理报告诊断为携带BRAFV600突变的Ⅲ期黑色素瘤患者进行回顾性分析。粘膜黑色素瘤患者,或随访<6个月,或接受其他辅助治疗被排除。进行Pearson卡方检验或Fisher精确检验以用于不同佐剂组的单变量分析。Log-rank分析用于确定无复发生存(RFS)的预后因素。
结果:在我们的研究中发现了93例切除的III期黑色素瘤患者BRAFV600E突变,包括25名接受辅助抗PD-1免疫疗法(PD-1)的患者,25接受佐剂D+T,23接收V,和20例患者仅观察(OBS)。治疗组之间的基线特征,包括年龄,性别,亚型,一次厚度,溃疡,节点参与。D+T组未达到中位无复发生存期(RFS),V组15个月,PD-1组15个月,在OBS组工作10个月,分别。与OBS相比,所有其他三组都显示出从RFS中受益的趋势,而只有D+T达到统计学差异(p=0.002)。然而,与D+T相比,抗PD-1单药治疗也显示出明显更差的复发控制(p=0.032).
结论:对于具有BRAF突变的中国人III期黑色素瘤,与仅观察相比,新型靶向治疗和免疫疗法在无复发生存期方面均显示出潜在益处.双靶向D+T疗法可能仍然是辅助疗法的最佳选择,因为抗PD-1单一疗法在现实世界实践中未能报告等效疗效。
BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%-15% of acral or mucosal subtypes. Currently, immunotherapy with anti-PD-1 blockade and dual-targeted therapy with
Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3-year recurrence-free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti-PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF-mut melanoma in recent years. We conducted this retrospective
study to evaluate the efficacy of different treatments in the Chinese melanoma population.
Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow-up of <6 months, or receiving other adjuvant treatment were excluded. Pearson\'s chi-squared test or Fisher\'s exact test was performed for univariable analysis of the different adjuvant groups. Log-rank analysis was used to identify prognostic factors for relapse-free survival (RFS).
Ninety-three patients with resected stage III melanoma with BRAF V600E mutation were identified in our
study, including 25 patients receiving adjuvant anti-PD-1 immunotherapy (PD-1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation-only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse-free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD-1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti-PD-1 monotherapy also showed significantly worse relapse control (p = 0.032).
For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse-free survival compared to observation only. Dual-targeted D + T therapy may still be the best choice for adjuvant therapy because anti-PD-1 monotherapy has failed to report equivalent efficacy in real-world practice.