Department of Experimental Medicine, Sapienza University of Rome, Rome F-00161, Italy.
Cancer Research Center of Lyon, Inserm U1052, CNRS UMR5286, Lyon F-69008, France.
Eur J Endocrinol. 2024 Aug 5;191(2):251-261. doi: 10.1093/ejendo/lvae091.
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.
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.
Objective response and clinical and safety outcomes were assessed after 3 months and at the last available follow-up during TT.
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.
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.
BRAF/MEK 抑制剂的靶向治疗 (TT) 已成为颅咽管瘤 (PCP) 的潜在治疗方法。然而，缺乏大样本队列的标准化数据。本研究旨在评估 BRAF/MEK 抑制剂在 PCP 患者中的真实疗效和安全性。
这是一项回顾性的法国多中心研究，纳入了 2019 年 4 月至 2023 年 7 月期间接受 BRAF V600E 突变型 PCP 患者接受 BRAF/MEK 抑制剂联合达拉非尼和曲美替尼治疗的患者。
在 TT 后 3 个月和最后一次随访时评估客观反应和临床及安全性结局。
纳入了 16 名患者（8 名女性，平均年龄 50.5 ± 15.75 岁），其中 6 名接受新辅助治疗（NEO）用于不可切除肿瘤，8 名接受术后辅助治疗（ADJ），2 名接受多模式治疗失败后的姑息治疗（PAL）。在最后一次随访（平均 7.6 ± 5.3 个月）时，12 名患者表现出部分缓解，3 名患者表现出部分缓解，1 名患者病情稳定。NEO、ADJ 和 PAL 组的平均体积减少率分别为 88.9 ± 4.4%、73.3 ± 23.4%和 91.8 ± 4.3%。靶向治疗缓解了 5/5 例患者的头痛和 6/9 例患者的视力障碍；2/3 例患者的神经症状改善，1/4 例患者的体重减轻，2/14 例患者的内分泌功能恢复。62.5%的病例靶向治疗耐受性良好；5 例患者因不良反应停止治疗，3 例患者最终停止治疗。
在这项研究中，94%的患者对 TT 有部分缓解或更好的反应。不良反应是可以接受的。需要进一步的研究来建立标准化的方案；然而，这些结果支持在侵袭性 PCP 中采用 NEO 方法。
