The Nature and Management of Metastatic Melanoma After Progression on BRAF Inhibitors: Effects of Extended BRAF Inhibition
The Nature and Management of Metastatic Melanoma After Progression on BRAF Inhibitors: Effects of Extended BRAF Inhibition
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DOI：
10.1002/cncr.28851
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发表时间：
2014-10-15
期刊：
影响因子：
6.2
通讯作者：
Long, Georgina V.
中科院分区：
文献类型：
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作者：
Chan, Matthew M. K.;Haydu, Lauren E.;Long, Georgina V.
背景：v-raf 鼠肉瘤病毒癌基因同源物 B (BRAF) 抑制剂 (BRAFi) 药物达拉非尼 (dabrafenib) 和维莫非尼 (vemurafenib) 对 BRAF 突变的转移性黑色素瘤具有较高的缓解率；然而，50% 的患者在 7 个月后出现进展。在这项研究中，作者研究了 BRAFi 治疗中疾病进展 (PD) 的性质和管理，包括在疾病进展 (TBP) 后继续接受 BRAFi 治疗的患者的特征和结果。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，包括持续的 BRAFi TBP（超出实体瘤 [RECIST] 定义的 PD 反应评估标准 >28 天）。结果：114 名 BRAFi 治疗患者中有 95 名患有 PD。这95名患者中的53名（56%）仅在颅外部位进展，18%（95名患者中的17名）同时在颅内和颅外部位进展，16%（95名患者中的15名）仅在颅内部位进展。 95 名患有 PD 的患者中，有 29 名 (31%) 在单个部位或器官出现进展，48%（95 名患者中的 46 名）仅在现有转移中出现进展，18%（95 名患者中的 17 名）仅出现新转移。在 PD 时，95 名患者中的 35 名（37%）没有接受后续全身治疗，20%（95 名患者中的 19 名）改变了全身治疗，39%（95 名患者中的 37 名）继续 BRAFi TBP 中位时间为 97 天。 BRAFi TBP 和已知的预后因素（东部肿瘤合作组体能状态、乳酸脱氢酶、RECIST 靶病灶最大尺寸总和）与 PD 时的总生存期 (OS) 相关；然而，在多变量分析中，BRAFi TBP 改善了 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出现进展，31% 在孤立部位出现进展。与停止治疗相比，即使在调整 PD 时的潜在预后因素后，持续 BRAFi TBP 仍与延长 OS 相关。 (C) 2014 年美国癌症协会。
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 mono-therapy 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. (C) 2014 American Cancer Society.