Hyman, David M., Puzanov, Igor, Subbiah, Vivek ORCID: 0000-0002-6064-6837, Faris, Jason E., Chau, Ian ORCID: 0000-0003-0286-8703, Blay, Jean-Yves ORCID: 0000-0001-7190-120X, Wolf, Juergen, Raje, Noopur S., Diamond, Eli L., Hollebecque, Antoine ORCID: 0000-0003-2869-7551, Gervais, Radj, Elena Elez-Fernandez, Maria, Italiano, Antoine, Hofheinz, Ralf-Dieter, Hidalgo, Manuel, Chan, Emily, Schuler, Martin, Lasserre, Susan Frances, Makrutzki, Martina, Sirzen, Florin, Veronese, Maria Luisa, Tabernero, Josep ORCID: 0000-0002-2495-8139 and Baselga, Jose (2015). Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N. Engl. J. Med., 373 (8). S. 726 - 737. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

BACKGROUND BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 basket study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers. METHODS We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival. RESULTS In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma. CONCLUSIONS BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hyman, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puzanov, IgorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Subbiah, VivekUNSPECIFIEDorcid.org/0000-0002-6064-6837UNSPECIFIED
Faris, Jason E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chau, IanUNSPECIFIEDorcid.org/0000-0003-0286-8703UNSPECIFIED
Blay, Jean-YvesUNSPECIFIEDorcid.org/0000-0001-7190-120XUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raje, Noopur S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diamond, Eli L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hollebecque, AntoineUNSPECIFIEDorcid.org/0000-0003-2869-7551UNSPECIFIED
Gervais, RadjUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elena Elez-Fernandez, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Italiano, AntoineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofheinz, Ralf-DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hidalgo, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chan, EmilyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuler, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lasserre, Susan FrancesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Makrutzki, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sirzen, FlorinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veronese, Maria LuisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tabernero, JosepUNSPECIFIEDorcid.org/0000-0002-2495-8139UNSPECIFIED
Baselga, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-396294
DOI: 10.1056/NEJMoa1502309
Journal or Publication Title: N. Engl. J. Med.
Volume: 373
Number: 8
Page Range: S. 726 - 737
Date: 2015
Publisher: MASSACHUSETTS MEDICAL SOC
Place of Publication: WALTHAM
ISSN: 1533-4406
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ERDHEIM-CHESTER DISEASE; LANGERHANS CELL HISTIOCYTOSIS; METASTATIC COLORECTAL-CANCER; LUNG-CANCER; 1ST-LINE TREATMENT; HIGH PREVALENCE; CHEMOTHERAPY; TRIAL; EGFR; INHIBITIONMultiple languages
Medicine, General & InternalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39629

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