BRAF 抑制剂治疗进展后的转移性黑色素瘤的性质和管理：延长 BRAF 抑制的效果。
The nature and management of metastatic melanoma after progression on BRAF inhibitors: effects of extended BRAF inhibition.
机构信息
Melanoma Institute Australia, Sydney, New South Wales, Australia; Department of Medical Oncology, Crown Princess Mary Cancer Center, Westmead Hospital, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia.
出版信息
Cancer. 2014 Oct 15;120(20):3142-53. doi: 10.1002/cncr.28851. Epub 2014 Jul 1.
BACKGROUND
The v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor (BRAFi) drugs dabrafenib and vemurafenib have high response rates in BRAF-mutant, metastatic melanoma; however, 50% of patients progress by 7 months. In this study, the authors examined the nature and management of disease progression (PD) on BRAFi treatment, including characteristics and outcomes of patients who received continued BRAFi treatment beyond disease progression (TBP).
METHODS
Clinicopathologic data at baseline and at the time of PD were collected for all patients with BRAF-mutant metastatic melanoma who received BRAFi monotherapy within clinical trials between July 2009 and September 2012. Management and survival after PD were examined, including continued BRAFi TBP (> 28 days beyond Response Evaluation Criteria in Solid Tumor [RECIST]-defined PD).
RESULTS
Ninety-five of 114 BRAFi-treated patients had PD. Fifty-three of those 95 patients (56%) progressed in extracranial sites alone, 18% (17 of 95 patients) progressed in intracranial and extracranial sites simultaneously, and 16% (15 of 95 patients) progressed in intracranial sites alone. Twenty-nine of the 95 patients (31%) who had PD progressed in a single site or organ, 48% (46 of 95 patients) progressed in existing metastases only, and 18% (17 of 95 patients) had new metastases alone. At the time of PD, 35 of 95 patients (37%) received no subsequent systemic treatment, 20% (19 of 95 patients) changed systemic treatments, and 39% (37 of 95 patients) continued BRAFi TBP for a median of 97 days. BRAFi TBP and known prognostic factors (Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, RECIST sum of the greatest dimensions of target lesions) were associated with overall survival (OS) from the time of PD; however, in multivariable analysis, BRAFi TBP improved OS (hazard ratio, 0.50; 95% confidence interval, 0.27-0.93; P = .029).
CONCLUSIONS
Most BRAFi-treated patients progressed in existing extracranial sites, and 31% progressed in isolated sites. Compared with cessation, continued BRAFi TBP is associated with prolonged OS even after adjusting for potential prognostic factors at PD.
背景
v-raf 鼠肉瘤病毒癌基因同源物 B（BRAF）抑制剂（BRAFi）药物 dabrafenib 和 vemurafenib 在 BRAF 突变、转移性黑色素瘤中具有高反应率；然而，50%的患者在 7 个月内进展。在这项研究中，作者研究了 BRAFi 治疗期间疾病进展（PD）的性质和管理，包括接受 BRAFi 治疗超过 PD（TBP）的患者的特征和结局。
方法
收集 2009 年 7 月至 2012 年 9 月期间在临床试验中接受 BRAFi 单药治疗的所有 BRAF 突变转移性黑色素瘤患者的基线和 PD 时的临床病理数据。检查 PD 后的管理和生存情况，包括接受 BRAFi TBP（在 RECIST 定义的 PD 后超过 28 天）。
结果
95 例接受 BRAFi 治疗的患者中有 95 例发生 PD。其中 53 例（56%）仅在颅外部位进展，18%（95 例患者中有 17 例）同时在颅内和颅外部位进展，16%（95 例患者中有 15 例）仅在颅内部位进展。29 例（31%）PD 患者的单一部位或器官进展，48%（95 例患者中有 46 例）仅在现有转移灶进展，18%（95 例患者中有 17 例）仅有新转移灶。在 PD 时，35 例（37%）患者未接受后续全身治疗，20%（95 例患者中有 19 例）改变了全身治疗，39%（95 例患者中有 37 例）继续 BRAFi TBP 治疗，中位数为 97 天。BRAFi TBP 和已知的预后因素（东部合作肿瘤组表现状态、乳酸脱氢酶、RECIST 靶病变最大直径总和）与 PD 后总生存期（OS）相关；然而，多变量分析显示，BRAFi TBP 可改善 OS（风险比，0.50；95%置信区间，0.27-0.93；P =.029）。
结论
大多数接受 BRAFi 治疗的患者在现有颅外部位进展，31%的患者在孤立部位进展。与停止治疗相比，即使在调整 PD 时的潜在预后因素后，继续 BRAFi TBP 治疗与延长 OS 相关。
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