Concurrent BRAF/MEK Inhibitors in BRAF V600-Mutant High-Grade Primary Brain Tumors
Concurrent BRAF/MEK Inhibitors in BRAF V600-Mutant High-Grade Primary Brain Tumors
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DOI：
10.6004/jnccn.2017.7052
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发表时间：
2018-04-01
影响因子：
13.4
通讯作者：
Grossman, Stuart A.
中科院分区：
文献类型：
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作者：
Schreck, Karisa C.;Guajardo, Andrew;Grossman, Stuart A.
随着分子检测的广泛应用，BRAF V600突变在原发性脑肿瘤患者中的发现越来越多。在个别病例中尝试了BRAF抑制剂的靶向治疗，其中一些病例有反应，而另一些病例则没有反应或出现耐药性。临床前研究表明，胶质瘤可能对同时使用BRAF和MEK抑制MAP激酶通路抑制更敏感。本报告介绍了2例BRAF V600 E突变的恶性脑肿瘤，对放射和替莫唑胺耐药，并报告了其对BRAF和MEK抑制剂达拉菲尼和曲美替尼靶向治疗的反应。1例间变性多形性黄色星形细胞瘤患者在14个月内出现部分缓解，表现为进行性肿瘤缩小和临床改善;然而，随后出现临床和影像学进展。胶质母细胞瘤患者在治疗16个月后病情持续稳定。这些病例在一种迫切需要新治疗方法的疾病中令人鼓舞。进一步的工作是必要的，以了解在原发性脑肿瘤的反应率，持续时间和生存。
BRAF V600 mutations are being identified in patients with primary brain tumors more often as molecular testing becomes widely available. Targeted treatment with BRAF inhibitors has been attempted in individual cases with some responses, whereas others showed no response or developed resistance. Preclinical work suggests that gliomas could be more responsive to the concurrent use of BRAF and MEK inhibition for MAP kinase pathway suppression. This report presents 2 cases of malignant brain tumors with BRAF V600E mutations that were resistant to radiation and temozolomide, and reports on their response to targeted treatment with the BRAF and MEK inhibitors dabrafenib and trametinib. One patient with an anaplastic pleomorphic xanthoastrocytoma experienced a partial response for 14 months, demonstrated by progressive tumor shrinkage and clinical improvement; however, this was followed by clinical and radiographic progression. The patient with glioblastoma continued to have stable disease after 16 months of treatment. These cases are encouraging in a disease that urgently needs new treatments. Further work is necessary to understand response rates, duration, and survival in primary brain tumors.