PMID- 29188284
OWN - NLM
STAT- MEDLINE
DCOM- 20190911
LR  - 20220410
IS  - 2374-2445 (Electronic)
IS  - 2374-2437 (Print)
IS  - 2374-2437 (Linking)
VI  - 4
IP  - 3
DP  - 2018 Mar 1
TI  - Vemurafenib for BRAF V600-Mutant Erdheim-Chester Disease and Langerhans Cell 
      Histiocytosis: Analysis of Data From the Histology-Independent, Phase 2, 
      Open-label VE-BASKET Study.
PG  - 384-388
LID - 10.1001/jamaoncol.2017.5029 [doi]
AB  - 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.
FAU - Diamond, Eli L
AU  - Diamond EL
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Subbiah, Vivek
AU  - Subbiah V
AD  - MD Anderson Cancer Center, Houston, Texas.
FAU - Lockhart, A Craig
AU  - Lockhart AC
AD  - Sylvester Comprehensive Cancer Center and University of Miami Miller School of 
      Medicine, Miami.
FAU - Blay, Jean-Yves
AU  - Blay JY
AD  - Centre Leon Berard, Lyon, France.
FAU - Puzanov, Igor
AU  - Puzanov I
AD  - Roswell Park Cancer Institute, Buffalo, New York.
FAU - Chau, Ian
AU  - Chau I
AD  - Royal Marsden Hospital, Sutton, Surrey, England.
FAU - Raje, Noopur S
AU  - Raje NS
AD  - Massachusetts General Hospital, Boston.
FAU - Wolf, Jurgen
AU  - Wolf J
AD  - University Hospital Koln, Koln, Germany.
FAU - Erinjeri, Joseph P
AU  - Erinjeri JP
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Torrisi, Jean
AU  - Torrisi J
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Lacouture, Mario
AU  - Lacouture M
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Elez, Elena
AU  - Elez E
AD  - Vall d'Hebron University Hospital and Institute of Oncology (VHIO) and 
      Universitat Autonoma de Barcelona, Barcelona, Spain.
FAU - Martinez-Valle, Ferran
AU  - Martinez-Valle F
AD  - Vall d'Hebron University Hospital and Institute of Oncology (VHIO) and 
      Universitat Autonoma de Barcelona, Barcelona, Spain.
FAU - Durham, Benjamin
AU  - Durham B
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Arcila, Maria E
AU  - Arcila ME
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Ulaner, Gary
AU  - Ulaner G
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Abdel-Wahab, Omar
AU  - Abdel-Wahab O
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Pitcher, Bethany
AU  - Pitcher B
AD  - Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada.
FAU - Makrutzki, Martina
AU  - Makrutzki M
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Riehl, Todd
AU  - Riehl T
AD  - Genentech Inc, South San Francisco, California.
FAU - Baselga, Jose
AU  - Baselga J
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
FAU - Hyman, David M
AU  - Hyman DM
AD  - Memorial Sloan Kettering Cancer Center, New York, New York.
AD  - Weill Cornell Medical College, New York, New York.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA201247/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - JAMA Oncol
JT  - JAMA oncology
JID - 101652861
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 207SMY3FQT (Vemurafenib)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - HG18B9YRS7 (Valine)
SB  - IM
EIN - JAMA Oncol. 2019 Jan 1;5(1):122. PMID: 30422161
CIN - JAMA Oncol. 2019 Jan 1;5(1):118-119. PMID: 30422162
MH  - Aged
MH  - Amino Acid Substitution/genetics
MH  - Erdheim-Chester Disease/diagnosis/*drug therapy/*genetics/mortality
MH  - Female
MH  - Fluorodeoxyglucose F18
MH  - Histiocytosis, Langerhans-Cell/diagnosis/*drug therapy/genetics/mortality
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Positron Emission Tomography Computed Tomography
MH  - Prognosis
MH  - Proto-Oncogene Proteins B-raf/*genetics
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Valine/genetics
MH  - Vemurafenib/*therapeutic use
PMC - PMC5844839
MID - NIHMS933869
COIS- Conflict of Interest Disclosures: Dr Subbiah reports grants from Roche/Genentech 
      during the conduct of the study; grants from Novartis, Bayer, GSK, Bluprint 
      Medicines, LOXO, Fujifilm, NCI-CTEP, and the NCCN outside the submitted work. Dr 
      Blay reports grants, personal fees and nonfinancial support from Roche, grants 
      from GSK, and grants and personal fees from Novartis during the conduct of the 
      study. Dr Puzanov reports personal fees from Roche during the conduct of the 
      study and personal fees from Amgen outside the submitted work. Dr Chau reports 
      grants and personal fees from Sanofi Oncology, personal fees from Eli-Lilly, 
      Bristol-Myers Squibb, MSD, Bayer, Roche, Five Prime Therapeutics, Taiho, Pfizer, 
      Amgen, and Gilead Science, and grants from Janssen-Cilag, Merck-Serono, and 
      Novartis, outside the submitted work. Dr Wolf reports research grants from 
      AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly, MSD, 
      Novartis, Pfizer, Roche, BMS, MSD, Novartis, Pfizer, and advisory boards and 
      lecture fees from Roche, outside the submitted work. Dr Lacouture reports 
      research grants and consulting fees from Genentech/Roche, research grants from 
      BMS, personal fees from Foamix, Debio, Janssen, Galderma, and Adgero, outside the 
      submitted work. Dr Martinez-Valle reports grants from Pfizer, outside the 
      submitted work. Dr Pitcher is an employee of F. Hoffmann-La Roche Ltd, 
      Mississauga, Ontario, Canada. Dr Makrutzki is an employee of F. Hoffmann-La Roche 
      Ltd, Basel, Switzerland. Dr Riehl is an employee of F. Hoffmann-La Roche Ltd and 
      owns stock in F. Hoffmann-La Roche Ltd. Dr Hyman reports personal fees from Atara 
      Biotherapeutics, Chugai Pharma, CytomX Therapeutics, Boehringer Ingelheim, and 
      AstraZeneca; and grants from AstraZeneca, Puma Biotechnology, and Loxo Oncology 
      outside the submitted work. No other disclosures are reported.
EDAT- 2017/12/01 06:00
MHDA- 2019/09/12 06:00
PMCR- 2018/11/29
CRDT- 2017/12/01 06:00
PHST- 2017/12/01 06:00 [pubmed]
PHST- 2019/09/12 06:00 [medline]
PHST- 2017/12/01 06:00 [entrez]
PHST- 2018/11/29 00:00 [pmc-release]
AID - 2664827 [pii]
AID - cbr170036 [pii]
AID - 10.1001/jamaoncol.2017.5029 [doi]
PST - ppublish
SO  - JAMA Oncol. 2018 Mar 1;4(3):384-388. doi: 10.1001/jamaoncol.2017.5029.