1St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri.
2Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Texas.
J Natl Compr Canc Netw. 2022 Nov;20(11):1193-1202.e6. doi: 10.6004/jnccn.2022.7046.
Recurrent and anaplastic pleomorphic xanthoastrocytoma (r&aPXA) is a rare primary brain tumor that is challenging to treat. Two-thirds of PXA tumors harbor a BRAF gene mutation. BRAF inhibitors have been shown to improve tumor control. However, resistance to BRAF inhibition develops in most cases. Concurrent therapy with MEK inhibitors may improve tumor control and patient survival. In this study, we identified 5 patients diagnosed with BRAF-mutated PXA who received BRAF and MEK inhibitors over a 10-year interval at our institution. Patient records were evaluated, including treatments, adverse effects (AEs), outcomes, pathology, next-generation sequencing, and MRI. The median age was 22 years (range, 14-66 years), 60% male, and 60% anaplastic PXA. Median overall survival was 72 months (range, 19-112 months); 1 patient died of tumor-related hemorrhage while off therapy, and the other 4 experienced long-term disease control (21, 72, 98, and 112 months, respectively). Dual BRAF/MEK inhibitors were well tolerated, with only grade 1-2 AEs, including rash, neutropenia, fatigue, abdominal discomfort, and diarrhea. No grade 3-5 AEs were detected. A literature review was also performed of patients diagnosed with BRAF-mutated PXA and treated with BRAF and/or MEK inhibitors through August 2021, with a total of 32 cases identified. The median age was 29 years (range, 8-57 years) and the median PFS and OS were 8.5 months (range, 2-35 months) and 35 months (range, 10-80 months), respectively. The most common AEs were grade 1-2 fatigue and skin rash. Results of this case series and literature review indicate that dual-drug therapy with BRAF and MEK inhibitors for r&aPXA with BRAF V600E mutation may delay tumor progression without unexpected AEs.
复发性和间变性多形性黄色星形细胞瘤（r&aPXA）是一种罕见的原发性脑肿瘤，治疗具有挑战性。三分之二的 PXA 肿瘤存在 BRAF 基因突变。BRAF 抑制剂已被证明可以改善肿瘤控制。然而，大多数情况下都会出现对 BRAF 抑制的耐药性。同时使用 MEK 抑制剂可能会改善肿瘤控制和患者生存。在这项研究中，我们确定了在我们机构的 10 年内接受 BRAF 和 MEK 抑制剂治疗的 5 名 BRAF 突变型 PXA 患者。评估了患者的记录，包括治疗、不良反应 (AE)、结果、病理、下一代测序和 MRI。中位年龄为 22 岁（范围，14-66 岁），60%为男性，60%为间变性 PXA。中位总生存期为 72 个月（范围，19-112 个月）；1 例患者在停药期间因肿瘤相关出血而死亡，其余 4 例患者长期疾病控制（分别为 21、72、98 和 112 个月）。双重 BRAF/MEK 抑制剂耐受性良好，仅出现 1-2 级 AE，包括皮疹、中性粒细胞减少症、疲劳、腹部不适和腹泻。未检测到 3-5 级 AE。还对 2021 年 8 月前通过 BRAF 和/或 MEK 抑制剂诊断为 BRAF 突变型 PXA 并接受治疗的患者进行了文献复习，共确定了 32 例。中位年龄为 29 岁（范围，8-57 岁），中位 PFS 和 OS 分别为 8.5 个月（范围，2-35 个月）和 35 个月（范围，10-80 个月）。最常见的 AE 为 1-2 级疲劳和皮疹。本病例系列和文献复习的结果表明，BRAF V600E 突变的 r&aPXA 采用 BRAF 和 MEK 抑制剂双重药物治疗可能会延迟肿瘤进展，而不会出现意外的 AE。
