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Brief Report
March 2018

Vemurafenib for BRAF V600–Mutant Erdheim-Chester Disease and Langerhans Cell HistiocytosisAnalysis of Data From the Histology-Independent, Phase 2, Open-label VE-BASKET Study

Author Affiliations
  • 1Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Weill Cornell Medical College, New York, New York
  • 3MD Anderson Cancer Center, Houston, Texas
  • 4Sylvester Comprehensive Cancer Center and University of Miami Miller School of Medicine, Miami
  • 5Centre Léon Bérard, Lyon, France
  • 6Roswell Park Cancer Institute, Buffalo, New York
  • 7Royal Marsden Hospital, Sutton, Surrey, England
  • 8Massachusetts General Hospital, Boston
  • 9University Hospital Köln, Köln, Germany
  • 10Vall d’Hebron University Hospital and Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain
  • 11Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada
  • 12F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • 13Genentech Inc, South San Francisco, California
JAMA Oncol. 2018;4(3):384-388. doi:10.1001/jamaoncol.2017.5029
Key Points

Questions  What are the long-term efficacy and safety of vemurafenib for adult patients with BRAF V600–mutant Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH)?

Findings  In a secondary analysis of data from and open-label nonrandomized study of 26 patients with BRAF V600–mutant ECD or LCH, vemurafenib had prolonged efficacy, with a 62% confirmed overall response rate (Response Evaluation Criteria in Solid Tumors) and 100% positron-emission tomography response rate. Median progression-free survival was not reached, and the 2-year progression-free survival rate was 86%.

Meaning  Vemurafenib has clinically meaningful and highly durable activity in patients with BRAF V600–mutant ECD or LCH, warranting its consideration as a new standard of care for these patients.


Importance  The histiocytic neoplasms Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are highly enriched for BRAF V600 mutations and have been previously shown to be responsive to treatment with vemurafenib, an inhibitor of the BRAF V600 kinase. However, the long-term efficacy and safety of prolonged vemurafenib use in these patients are not defined. Here we analyze the final efficacy and safety data for vemurafenib in patients with ECD and LCH enrolled in the VE-BASKET study.

Objective  To determine the efficacy and safety of vemurafenib in adults with ECD or LCH enrolled in the VE-BASKET study.

Design, Setting, and Participants  The VE-BASKET study was an open-label, nonrandomized, multicohort study for patients with nonmelanoma cancers harboring the BRAF V600 mutation. Patients with BRAF V600–mutant ECD or LCH were enrolled in an “other solid tumor” cohort of the VE-BASKET study, and they were enrolled in the present study.

Interventions  Patients received vemurafenib, 960 mg, twice daily continuously until disease progression, study withdrawal, or occurrence of intolerable adverse effects.

Main Outcomes and Measures  The primary end point was confirmed objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Secondary end points included progression-free survival (PFS), overall survival (OS), metabolic response by modified positron-emission tomography (PET) Response Criteria in Solid Tumors (PERCIST) using 18F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT), and safety.

Results  A total of 26 patients from the VE-BASKET trial (22 with ECD, 4 with LCH) were included in the present study (14 women and 12 men; median age, 61 years; age range, 51-74 years). The confirmed ORR was 61.5% (95% CI, 40.6%-79.8%) in the overall cohort and 54.5% (95% CI, 32.2%-75.6%) in patients with ECD. All evaluable patients achieved stable disease or better. The median PFS and OS had not been reached in the overall cohort at study closure despite a median follow-up of 28.8 months; 2-year PFS was 86% (95% CI, 72%-100%), and 2-year OS was 96% (95% CI, 87%-100%). All 15 patients evaluated by FDG-PET/CT achieved a metabolic response, including 12 patients (80%) with a complete metabolic response. The most common adverse events (AEs) in the overall cohort included arthralgia, maculopapular rash, fatigue, alopecia, prolonged QT interval, skin papilloma, and hyperkeratosis. Hypertension and dermatologic AEs occurred at higher rates than those reported in metastatic melanoma.

Conclusions and Relevance  In this study, vemurafenib had prolonged efficacy in patients with BRAF V600–mutant ECD and LCH and warrants consideration as a new standard of care for these patients.