Patterns of Response and Progression in Patients With BRAF-Mutant Melanoma Metastatic to the Brain Who Were Treated With Dabrafenib
Patterns of Response and Progression in Patients With BRAF-Mutant Melanoma Metastatic to the Brain Who Were Treated With Dabrafenib
复制标题
DOI：
10.1002/cncr.28445
复制
发表时间：
2014-02-15
期刊：
影响因子：
6.2
通讯作者：
Long, Georgina V.
中科院分区：
文献类型：
--
作者：
Azer, Mary W. F.;Menzies, Alexander M.;Long, Georgina V.
背景达拉非尼对脑转移患者有活性，但对脑内和脑外治疗的相对疗效知之甚少。本研究旨在探讨颅内（IC）和颅外（EC）模式的反应和进展与dabrafenib. METHODS治疗的活动性黑色素瘤脑转移瘤患者的临床病理学参数收集在一个单一的机构参加dabrafenib的1期和2期研究的活动性脑转移瘤患者。按疾病部位（IC vs EC）前瞻性评估了RECIST（实体瘤疗效评价标准）缓解和无进展生存期（PFS）。对疾病进展后接受的治疗也进行了评估。共有23例患者接受了研究。IC（78%）和EC（90%）中心的缓解率相似（P= 0.416）。71%的患者IC和EC反应一致。IC和EC研究中心的中位研究中心特异性PFS相同（23.6周，P= 0.465），超过了RECIST确定的全身PFS（16.3周）。在20例疾病进展（PD）患者中，6例仅发生IC PD，6例仅发生EC PD，8例在两个部位均发生PD。在那些孤立的颅内PD，5 6进行了局部治疗的大脑，并继续对dabrafenib超过30 day.CONCLUSIONSIC和EC黑色素瘤转移反应相似，达拉菲尼。在接受达拉非尼治疗的脑转移瘤患者中，没有明显的疾病进展部位或模式。在IC疾病进展后，大多数患者可以进行挽救性局部治疗，在一部分患者中可以进行持续的达拉非尼治疗。Cancer 2014;120：530-536. (c)2013年美国癌症协会
BACKGROUNDDabrafenib has activity in patients with brain metastases, but little is known of the relative efficacy of treatment within and outside the brain. This study sought to examine the intracranial (IC) and extracranial (EC) patterns of response and progression in patients with active melanoma brain metastases treated with dabrafenib.METHODSClinicopathologic parameters were collected on patients with active brain metastases enrolled in the phase 1 and 2 studies of dabrafenib at a single institution. RECIST (Response Evaluation Criteria In Solid Tumors) response and progression-free survival (PFS) were prospectively assessed by disease site (IC versus EC). Treatments received after disease progression were also assessed.RESULTSA total of 23 patients were studied. Response rates were similar in IC (78%) and EC (90%) sites (P=.416). IC and EC response was concordant in 71% of patients. Median site-specific PFS was identical in both IC and EC sites (23.6 weeks, P=.465), and exceeded whole-body PFS determined by RECIST (16.3 weeks). Of 20 patients with progressive disease (PD), 6 had IC PD only, 6 had EC PD only, and 8 had PD in both sites. In those with isolated intracranial PD, 5 of 6 underwent local therapy to the brain and continued on dabrafenib longer than 30 days.CONCLUSIONSIC and EC melanoma metastases respond similarly to dabrafenib. There is no dominant site or pattern of disease progression in patients with brain metastases treated with dabrafenib. Salvage local therapy is possible in most patients after IC disease progression, with ongoing dabrafenib treatment possible in a subset of patients. Cancer 2014;120:530-536. (c) 2013 American Cancer Society.