Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2018 Dec;23(12):1520-1524. doi: 10.1634/theoncologist.2018-0295. Epub 2018 Aug 17.
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 V600 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 V600E 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 V600 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 V600 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.
2017 年 11 月 6 日，美国食品和药物管理局（FDA）批准威罗非尼用于治疗 V600 突变的 Erdheim-Chester 病（ECD）成年患者。ECD 是组织细胞增多症的一种类型，是一种罕见的疾病，其特征是单核吞噬细胞系统的细胞异常积聚和行为异常，包括抗原处理细胞、树突状细胞、单核细胞或巨噬细胞。最近发表的数据证实，ECD 患者 V600E 突变的频率为 54%。该批准基于 VE 篮子试验（MO28072）中的 22 名接受每日两次 960mg 威罗非尼治疗的患者队列，这是一项单臂、多中心、多队列研究。ECD 队列的患者经组织学证实患有 ECD，且对标准治疗有抗药性。ECD 队列的总缓解率为 54.5%（95%置信区间：32.2-75.6），完全缓解率为 4.5%。中位随访 26.6 个月时，中位缓解持续时间尚未达到。ECD 队列中报告的最常见不良反应（>50%）为关节痛、斑丘疹性皮疹、脱发、疲劳、心电图 QT 间期延长和皮肤乳头状瘤。该研究中 ECD 患者的中位治疗持续时间为 14.2 个月。本文描述了 FDA 对威罗非尼治疗 ECD 患者的疗效补充的审查，这些患者存在 V600 突变。对实践的影响：威罗非尼是一种针对 BRAF 突变的口服单药治疗药物，是美国 FDA 批准的第一种治疗 Erdheim-Chester 病（ECD）的药物。ECD 是一种极其罕见的造血肿瘤，代表骨髓祖细胞的克隆性增殖。ECD 可能累及骨骼和一个或多个器官系统，主要影响 50 至 70 岁的成年人，男性略占优势。这一批准为患有严重危及生命的疾病且无获批治疗方案的患者提供了一种有效且相对安全的治疗方法。
