Acute Kidney Injury Following Encorafenib and Binimetinib for Metastatic Melanoma.
Acute Kidney Injury Following Encorafenib and Binimetinib for Metastatic Melanoma.
复制标题
恩科拉非尼和比尼美替尼治疗转移性黑色素瘤后的急性肾损伤。
DOI：
10.1016/j.xkme.2020.01.012
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发表时间：
2020
期刊：
影响因子：
3.9
通讯作者：
Sise,MeghanE
中科院分区：
文献类型：
--
作者：
Seethapathy,Harish;Bates,Halla;Chute,DonaldF;Strohbehn,Ian;Strohbehn,Samuel;Fadden,RileyM;Reynolds,KerryL;Cohen,JustineV;Sullivan,RyanJ;Sise,MeghanE
肾毒性是 BRAF 抑制剂的一个重要不良反应，BRAF 抑制剂是治疗晚期 BRAF V600 突变转移性黑色素瘤的主要药物。 1, 2, 3 Encorafenib 是此类新药，最近被批准与 MEK 抑制剂 binimetinib 联合治疗晚期转移性黑色素瘤患者。 4, 5 在该组合的 1 期试验中，encorafenib 的最大耐受剂量为每日 450 mg 和每日 600 mg，但 450 mg 成为美国食品和药物管理局批准的剂量，因为 3 名患者在较高剂量下出现不明原因的急性肾损伤 (AKI)。 6 在晚期黑色素瘤患者联合用药的 3 期 COLUMBUS 试验中，高达 93% 的参与者肌酐水平至少增加了 0.3 mg/dL。 4, 5 我们旨在描述接受 encorafenib-binimetinib 治疗恶性黑色素瘤的患者中 AKI 的发生率、发生时间和临床特征。我们回顾性分析了 2013 年至 2019 年间在 Partners Healthcare 接受 encorafenib-binimetinib 的所有患者的数据。使用研究患者数据注册表，通过药物列表和电子健康记录的自然语言处理搜索“encorafenib”、“binimetinib”或“enco-bini。”通过图表审查，我们记录了基线人口统计数据、合并症、药物、实验室研究以及恩科拉非尼-binimetinib 剂量和开始日期。对患者进行了为期 1 年的随访。肾脏疾病：改善全球结局 (KDIGO) 标准用于 AKI 的诊断和分级。 7 AKI 的病因由 2 名肾病专家（HS 和 MES）确定。短暂性 AKI 定义为通过支持措施在 48 小时内缓解的 AKI。尽管采取了支持措施，持续的 AKI 仍持续超过 48 小时。使用单变量逻辑回归来比较与 AKI 相关的基线人口统计学和临床特征。
Nephrotoxicity is an important adverse effect of BRAF inhibitors, a class of drugs that are a mainstay for the treatment of advanced BRAF V600-mutant metastatic melanoma. 1, 2, 3 Encorafenib, a new drug in this class, has recently been approved in combination with binimetinib, a MEK inhibitor, for patients with advanced metastatic melanoma. 4, 5 In the phase 1 trial of this combination, the maximum tolerated doses of encorafenib were 450 mg daily and 600 mg daily, but 450 mg became the US Food and Drug Administration–approved dose because 3 patients had unexplained acute kidney injury (AKI) at the higher dose. 6 Up to 93% of participants in the phase 3 COLUMBUS trial of the combination in patients with advanced melanoma experienced at least a 0.3-mg/dL increase in creatinine level. 4, 5 We aimed to describe the incidence, timing, and clinical features of AKI in patients receiving encorafenib-binimetinib for malignant melanoma.We retrospectively analyzed data from all patients who received encorafenib-binimetinib at Partners Healthcare between 2013 and 2019. Patients were identified using the Research Patient Data Registry by both medication list and natural language processing of electronic health records searching for “encorafenib,”“binimetinib,” or “enco-bini.” Using chart review, we recorded baseline demographics, comorbid conditions, medications, laboratory studies, and encorafenib-binimetinib dose and start date. Patients were followed up for 1 year. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to diagnose and grade AKI. 7 The cause of AKI was determined by 2 nephrologists (HS and MES). Transient AKI was defined as AKI that resolved with supportive measures in less than 48 hours. Sustained AKI persisted longer than 48 hours despite supportive measures. Univariable logistic regression was used to compare the baseline demographic and clinical characteristics associated with AKI.