Real-World Toxicity Experience with BRAF/MEK Inhibitors in Patients with Erdheim-Chester Disease. Oncologist 2020 Feb;25(2):e386-e390
Date
02/12/2020Pubmed ID
32043767Pubmed Central ID
PMC7011668DOI
10.1634/theoncologist.2019-0606Scopus ID
2-s2.0-85075299733 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. The BRAF inhibitor vemurafenib is approved by the U.S. Food and Drug Administration (FDA) for patients with ECD harboring a BRAF V600E mutation. Successful treatment has also been reported with MEK-targeted therapies, likely because of the fact that BRAF mutant-negative patients harbor MEK pathway alterations. In our Rare Tumor Clinic, we noted that these patients have frequent drug-related toxicity, consistent with previous reports indicating the need to markedly lower doses of interferon-alpha when that agent is used in these patients.
PATIENTS AND METHODS: We performed a review of ten patients with ECD seen at the Rare Tumor Clinic at University of California San Diego receiving 16 regimens of targeted BRAF, MEK, or combined therapies.
RESULTS: The median age of the ten patients with ECD was 53 years (range, 29-77); seven were men. The median dose percentage (percent of FDA-approved dose) tolerated was 25% (range, 25%-50%). The most common clinically significant adverse effects resulting in dose adjustments of targeted therapies were rash, arthralgias, and uveitis. Renal toxicity and congestive heart failure were seen in one patient each. In spite of these issues, eight of ten patients (80%) achieved a partial remission on therapy.
DISCUSSION: Patients with ECD appear to require substantially reduced doses of BRAF and MEK inhibitors but are responsive to these lower doses.
Author List
Saunders IM, Goodman AM, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Erdheim-Chester Disease
Female
Humans
Male
Middle Aged
Mitogen-Activated Protein Kinase Kinases
Mutation
Proto-Oncogene Proteins B-raf
