On November 6, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of adult patients with Erdheim-Chester disease (ECD) with BRAFV600 mutation. ECD is a type of histiocytosis, a rare disorder characterized by an abnormal accumulation and behavior of cells of the mononuclear phagocytic system, which includes antigen-processing cells, dendritic cells, monocytes, or macrophages. Recently published data confirm a frequency of 54% of BRAFV600E mutations in patients with ECD.Approval was based on a cohort of 22 patients who received 960 mg of vemurafenib twice daily within the VE Basket Trial (MO28072), a single-arm, multicenter, multiple cohort study. Patients in the ECD cohort had histologically confirmed ECD with BRAFV600 mutations that were refractory to standard therapy. The ECD cohort achieved an overall response rate of 54.5% (95% confidence interval: 32.2-75.6), with a complete response rate of 4.5%. With a median duration of follow-up of 26.6 months, the median duration of response has not been reached. The most frequently reported adverse reactions (>50%) in the ECD cohort were arthralgia, rash maculo-papular, alopecia, fatigue, electrocardiogram QT interval prolonged, and skin papilloma. The median treatment duration for ECD patients in this study was 14.2 months. This article describes the FDA review of the vemurafenib efficacy supplement for patients with ECD with BRAFV600 mutations. IMPLICATIONS FOR PRACTICE: Vemurafenib, an oral monotherapy targeting a mutation in BRAF, is the first U.S. Food and Drug Administration approval for the treatment of Erdheim-Chester disease (ECD). ECD is an extremely rare hematopoietic neoplasm that represents clonal proliferation of myeloid progenitor cells. ECD may involve bone and one or more organ systems, primarily affecting adults in their 5th and 7th decades of life, with a slight male predominance. This approval provides an effective and reasonably safe therapy for patients with a serious and life-threatening condition for which no approved therapy exists.
摘要
2017 年 11 月 6 日,美国食品和药品管理局 (FDA) 对用于治疗患有 BRAFV600 突变的 Erdheim‐Chester 病 (ECD) 成人患者的维罗非尼授予常规批准。ECD 是一种组织细胞增生症,这种罕见病以包括抗原提呈细胞、树突细胞、单核细胞或巨噬细胞的单核巨噬细胞系统的细胞异常积聚和行为为特征。最近发布的数据证实,ECD 患者的 BRAFV600E 突变发生率为 54%。
此项批准以一个 22 名患者的队列为依据,这些患者在 VE 篮型试验 (MO28072)(一个单组、多中心、多队列研究)中接受维罗非尼960 mg、每天给药 2 次的治疗。ECD 队列中的患者患有已在组织学上证实的 ECD 和 BRAFV600 突变,并在标准疗法中耐药。ECD 队列取得了 54.5% 的总缓解率(95% 置信区间:32.2–75.6),完全缓解率为 4.5%。随访的中位持续时间为 26.6 个月,未达到缓解的中位持续时间。在 ECD 队列中,最常报告的不良反应 (>50%) 为关节痛、斑状丘疹、脱发、疲劳、心电图 QT 间期延长以及皮肤乳头状瘤。在本次研究中,ECD 患者的中位治疗持续时间为 14.2 个月。本文描述了 FDA 对患有 BRAFV600 突变的 ECD 患者的维罗非尼疗效补充的评审
Keywords: BRAFV600 mutations; Histiocytosis; Non‐Langerhans cell histocytosis; Vemurafenib; Zelboraf.
Published 2018. This article is a U.S. Government work and is in the public domain in the USA.