目的:BRAF/MEK抑制剂的靶向治疗(TT)已成为乳头状颅咽管瘤(PCPs)的潜在治疗方法。然而,缺乏大型队列的标准化数据。我们的研究旨在评估BRAF/MEK抑制在PCPs患者中的实际疗效和安全性。
方法:涉及BRAFV600E突变的PCP患者的法国多中心回顾性研究,BRAF/MEK抑制剂联合达拉非尼和曲美替尼治疗,从2019年4月到2023年7月。
方法:在TT期间进行3个月和最后一次随访时,评估客观反应以及临床和安全性结果。
结果:16例患者(8例女性,平均年龄50.5±15.75岁),接受不可切除肿瘤的新辅助治疗(NEO)(n=6),术后辅助治疗(ADJ;n=8),或多模式治疗失败后的姑息治疗(PAL)(n=2),包括在内。末次随访(平均7.6±5.3个月),12例患者显示次全反应,3表现出部分反应,1维持病情稳定。平均体积减少为88.9±4.4%,73.3±23.4%,在NEO中为91.8±4.3%,ADJ,和PAL组,分别。靶向治疗解决了5/5患者的头痛和6/9的视力障碍;2/3的患者神经症状改善,1/4表示体重减轻,2/14内分泌功能恢复。62.5%的患者对靶向治疗具有良好的耐受性;5例患者出现不良事件导致治疗终止,3例患者出现最终终止治疗。
结论:在这项研究中,94%的患者对TT表现出部分反应或更好。不良事件是可以接受的。需要进一步的研究来建立标准化的协议;然而,这些结果主张在侵入性PCP中采用NEO方法。
OBJECTIVE: Targeted therapy (TT) with BRAF/MEK inhibitors has emerged as a potential treatment in papillary craniopharyngiomas (PCPs). However, standardized data on large cohorts are lacking. Our study aimed to assess real-life efficacy and safety of BRAF/MEK inhibition in patients with PCPs.
METHODS: Retrospective French multicenter study involving BRAF V600E-mutated PCP patients, treated with BRAF/MEK inhibitor combination dabrafenib and trametinib, from April 2019 to July 2023.
METHODS: Objective response and clinical and safety outcomes were assessed after 3 months and at the last available follow-up during TT.
RESULTS: Sixteen patients (8 females, mean age 50.5 ± 15.75 years), receiving either neoadjuvant therapy (NEO) for non-resectable tumors (n = 6), post-surgical adjuvant therapy (ADJ; n = 8), or palliative therapy (PAL) following failure of multimodal treatment (n = 2), were included.At the last follow-up (mean 7.6 ± 5.3 months), 12 patients showed subtotal response, 3 exhibited partial response, and 1 maintained stable disease. Mean volume reduction was 88.9 ± 4.4%, 73.3 ± 23.4%, and 91.8 ± 4.3% in the NEO, ADJ, and PAL groups, respectively.Targeted therapy resolved headaches in 5/5 patients and visual impairment in 6/9; 2/3 patients had improved neurological symptoms, 1/4 presented weight loss, and 2/14 recovered endocrine function.Targeted therapy was well-tolerated in 62.5% of cases; adverse events led to treatment discontinuation in 5 patients and definitive discontinuation in 3 cases.
CONCLUSIONS: In this study, 94% of patients showed partial response or better to TT. Adverse events were acceptable. Further research is needed to establish standardized protocols; however, these results advocate for a NEO approach in invasive PCPs.