FDA Approval Summary: Vemurafenib for the Treatment of Patients with Erdheim-Chester Disease with the BRAFV600 Mutation.

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.

The use of vemurafenib in Australian patients with unresectable or metastatic melanoma containing the V600 BRAF gene mutation.

Metastatic melanoma remains one of the major causes of death related to skin cancers and has been resistant to traditional anticancer therapies. The clinical development of vemurafenib in the treatment of metastatic melanoma with the V600 mutation of the BRAF gene has provided meaningful improvements in the overall survival and progression-free survival of metastatic melanoma patients. However, significant side effects have been noted with this therapy, in particular cutaneous adverse events (AEs) such as rashes, squamous cell carcinoma and severe photosensitivity to UVA light among others. With an emphasis on the Australian perspective, this review provides an overview of the clinical development of vemurafenib, its attendant dose-limiting toxicities and other AEs, recommendations for safety monitoring, supportive treatments of AEs and dose modifications, with the aim of maximizing the chances of continuing beneficial treatment.

Eruptive Nevi Mimicking Wart-Like Lesions under Selective BRAF Inhibition in a 37-Year-Old Female Melanoma Patient.

BACKGROUND: The BRAF inhibitor vemurafenib is state of the art in therapy of patients with malignant melanoma in non-resectable stage III or stage IV and evidence of oncogenetic BRAF mutation. Multiple cutaneous side effects like rash and keratoacanthoma-like lesions have been described so far. CASE REPORT: We report a patient who presented multiple wart-like lesions under therapy with vemurafenib. Histologically we have seen multiple melanocytic nevi with a wart-like appearance. One melanoma in situ developed on the left forearm. CONCLUSIONS: Eruptive nevi and induction of melanoma may be a further side effect in patients undergoing a therapy with BRAF inhibitors.