Universität zu Köln

Diamond, Eli L., Subbiah, Vivek ORCID: 0000-0002-6064-6837, Lockhart, A. Craig, Blay, Jean-Yves ORCID: 0000-0001-7190-120X, Puzanov, Igor, Chau, Ian, Raje, Noopur S., Wolf, Jurgen, Erinjeri, Joseph P., Torrisi, Jean, Lacouture, Mario, Elez, Elena ORCID: 0000-0002-4653-6324, Martinez-Valle, Ferran, Durham, Benjamin ORCID: 0000-0001-8090-5448, Arcila, Maria E., Ulaner, Gary, Abdel-Wahab, Omar, Pitcher, Bethany, Makrutzki, Martina, Riehl, Todd, Baselga, Jose and Hyman, David M. (2018). 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. JAMA Oncol., 4 (3). S. 384 - 389. CHICAGO: AMER MEDICAL ASSOC. ISSN 2374-2445

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Abstract

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, 960mg, 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 F-18-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Diamond, Eli L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Subbiah, Vivek UNSPECIFIED orcid.org/0000-0002-6064-6837 UNSPECIFIED Lockhart, A. Craig UNSPECIFIED UNSPECIFIED UNSPECIFIED Blay, Jean-Yves UNSPECIFIED orcid.org/0000-0001-7190-120X UNSPECIFIED Puzanov, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Chau, Ian UNSPECIFIED UNSPECIFIED UNSPECIFIED Raje, Noopur S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Erinjeri, Joseph P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Torrisi, Jean UNSPECIFIED UNSPECIFIED UNSPECIFIED Lacouture, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Elez, Elena UNSPECIFIED orcid.org/0000-0002-4653-6324 UNSPECIFIED Martinez-Valle, Ferran UNSPECIFIED UNSPECIFIED UNSPECIFIED Durham, Benjamin UNSPECIFIED orcid.org/0000-0001-8090-5448 UNSPECIFIED Arcila, Maria E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ulaner, Gary UNSPECIFIED UNSPECIFIED UNSPECIFIED Abdel-Wahab, Omar UNSPECIFIED UNSPECIFIED UNSPECIFIED Pitcher, Bethany UNSPECIFIED UNSPECIFIED UNSPECIFIED Makrutzki, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Riehl, Todd UNSPECIFIED UNSPECIFIED UNSPECIFIED Baselga, Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Hyman, David M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-193469
DOI:	10.1001/jamaoncol.2017.5029
Journal or Publication Title:	JAMA Oncol.
Volume:	4
Number:	3
Page Range:	S. 384 - 389
Date:	2018
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	2374-2445
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUTATIONS Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19346