A Retrospective Evaluation of Vemurafenib as Treatment for BRAF-Mutant Melanoma Brain Metastases
A Retrospective Evaluation of Vemurafenib as Treatment for BRAF-Mutant Melanoma Brain Metastases
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DOI：
10.1634/theoncologist.2014-0012
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发表时间：
2015-07-01
期刊：
影响因子：
5.8
通讯作者：
Chapman, Paul B.
中科院分区：
文献类型：
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作者：
Harding, James J.;Catalanotti, Federica;Chapman, Paul B.
背景RAF抑制剂是BRAF突变型黑色素瘤和脑转移患者的有效治疗方法。有效性数据来自于临床研究，这些研究中有生理健康的患者;因此，评估维罗非尼在该人群中的真实经验是有意义的。影响对RAF激酶抑制剂敏感性的肿瘤特异性遗传变异也需要研究。我们回顾了BRAF突变型黑色素瘤和脑转移瘤患者接受维罗非尼治疗的记录。提取临床数据以确定颅外和颅内客观缓解率、无进展生存期（PFS）、总生存期（OS）和安全性。使用诱饵捕获、下一代测序分析来鉴定治疗前肿瘤中的突变，这些突变可以解释对维罗非尼的原发性耐药。在接受维罗非尼治疗的颅内疾病患者中，27例患者被纳入生存分析，22例患者可评估缓解。颅外和颅内客观缓解率分别为71%和50%。在19例可评价患者中，4例在颅外和颅内转移部位之间观察到不一致的反应。中位PFS为4.1个月（95%置信区间[CI]：2.6-7.9）;中位颅内PFS为4.6个月（95% CI：2.7-7.9），中位OS为7.5个月（95% CI：4.3-未达到），1年OS率为30.4%。结果受性能状态的影响。Vemurafenib是可以耐受的，尽管在一些接受全脑放疗的患者中发生了放射性皮炎。为7名患者提供了足够的样本用于下一代测序分析。黑色素瘤归类为“敏感性差”（>= 20%肿瘤生长，新病变，或
Background. RAF inhibitors are an effective therapy for patients with BRAF-mutant melanoma and brain metastasis. Efficacy data are derived from clinical studies enriched with physiologically fit patients; therefore, it is of interest to assess the real-world experience of vemurafenib in this population. Tumor-specific genetic variants that influence sensitivity to RAF kinase inhibitors also require investigation.Methods. Records of patients with BRAF-mutant melanoma and brain metastases who were treated with vemurafenib were reviewed. Clinical data were extracted to determine extracranial and intracranial objective response rates, progression-free survival (PFS), overall survival (OS), and safety. A bait-capture, next-generation sequencing assay was used to identify mutations in pretreatment tumors that could explain primary resistance to vemurafenib.Results. Among patients with intracranial disease treated with vemurafenib, 27 were included in survival analyses and 22 patients were assessable for response. The extracranial and intracranial objective response rates were 71% and 50%, respectively. Discordant responses were observed between extracranial and intracranial metastatic sites in 4 of 19 evaluable patients. Median PFS was 4.1 months (95% confidence interval [CI]: 2.6-7.9); median intracranial PFS was 4.6 months (95% CI: 2.7-7.9), median OS was 7.5 months (95% CI: 4.3-not reached), with a 30.4% 1-year OS rate. Outcomes were influenced by performance status. Vemurafenib was tolerable, although radiation-induced dermatitis occurred in some patients who received whole-brain radiotherapy. Adequate samples for next-generation sequencing analysis were available for seven patients. Melanomas categorized as "poorly sensitive" (>= 20% tumor growth, new lesions, or