{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:19:26Z","timestamp":1787030366866,"version":"build-2736575974"},"reference-count":38,"publisher":"Innovative Healthcare Institute","issue":"1","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Intrahepatic cholangiocarcinoma is a rare malignancy, which is rich in actionable alterations. Genomic aberrations in the mitogen-activated protein kinase (MAPK) pathway are common, and BRAF exon 15 p.V600E mutations are present in 5\u20137% of biliary tract cancers (BTC). Dual inhibition of BRAF and MEK has been established for BRAF-mutated melanoma and lung cancer, and recent basket trials have shown efficacy of this combination in BRAF V600E-mutant BTCs. Here, we report on a patient with BRAF exon 15 p.V600E mutant metastatic intrahepatic cholangiocarcinoma who was started on BRAF and MEK inhibition with vemurafenib and combimetinib. Shortly thereafter, he developed debilitating myositis, which was refractory to corticosteroids, requiring therapeutic plasma exchange and intravenous immunoglobulin. We also review BRAF as a target in BTCs, relevant clinical trials, and adverse events associated with BRAF and MEK inhibition.<\/jats:p>","DOI":"10.36401\/jipo-21-18","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T14:27:52Z","timestamp":1643898472000},"page":"26-30","source":"Crossref","is-referenced-by-count":2,"title":["Corticosteroid-Refractory Myositis After Dual BRAF and MEK Inhibition in a Patient with BRAF V600E-Mutant Metastatic Intrahepatic Cholangiocarcinoma"],"prefix":"10.36401","volume":"5","author":[{"given":"Timothy P.","family":"DiPeri","sequence":"first","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Demirhan","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Department of Medicine, Elmhurst Hospital Center, Icahn School of Medicine at Mount Sinai, New York City, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Karp","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqing","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Subbiah","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joann","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leomar Y.","family":"Ballester","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston, TX, USA"},{"name":"Department of Neurosurgery, University of Texas Health Science Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean H.","family":"Tayar","sequence":"additional","affiliation":[{"name":"Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Suarez-Almazor","sequence":"additional","affiliation":[{"name":"Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milind","family":"Javle","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Funda","family":"Meric-Bernstam","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Department of Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"22027","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"2022031621185509000_i2590-017X-5-1-26-b01","unstructured":"Binimetinib.\n          Prescribing information. Array BioPharma Inc.; 2020. Accessed April 6, 2021.\n          \n            nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/6c3408ac-d401-4925-8a03-26591afbc240\/spl-doc?hl=binimetinib. Revised October 2020. Accessed April 6, 2021."},{"key":"2022031621185509000_i2590-017X-5-1-26-b02","unstructured":"Encorafenib.\n          Prescribing information. Array BioPharma Inc.; 2020. Accessed April 6, 2021.\n          \n            nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/235dfc38-0f0b-4037-b501-7a9f4294740c\/spl-doc?hl=encorafenib."},{"key":"2022031621185509000_i2590-017X-5-1-26-b03","unstructured":"Trametinib.\n          Prescribing information. Novartis Pharmaceuticals Corporation; 2020. Accessed April 6, 2021.\n          \n            nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/0002ad27-779d-42ab-83b5-bc65453412a1\/spl-doc?hl=trametinib"},{"key":"2022031621185509000_i2590-017X-5-1-26-b04","unstructured":"Dabrafenib.\n          Prescribing information. 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JCO Precis Oncol.\n          2020;\n\t\t\t\t\t4:\n\t\t\t\t\t557\u2013\n\t\t\t\t\t569.","DOI":"10.1200\/PO.18.00414"},{"key":"2022031621185509000_i2590-017X-5-1-26-b14","doi-asserted-by":"crossref","unstructured":"Davies\n              H,\n            \n            \n              Bignell\n              GR,\n            \n            \n              Cox\n              C,\n            \n            et al.\n          \n          Mutations of the BRAF gene in human cancer.\n\t\t\t\t\tNature.\n\t\t\t\t\t2002;\n\t\t\t\t\t417:\n\t\t\t\t\t949\u2013\n\t\t\t\t\t954.","DOI":"10.1038\/nature00766"},{"key":"2022031621185509000_i2590-017X-5-1-26-b15","doi-asserted-by":"crossref","unstructured":"Ascierto\n              PA,\n            \n            \n              Kirkwood\n              JM,\n            \n            \n              Grob\n              JJ,\n            \n            et al.\n          \n          The role of BRAF V600 mutation in melanoma.\n\t\t\t\t\tJ Transl Med.\n\t\t\t\t\t2012;\n\t\t\t\t\t10:\n\t\t\t\t\t85.","DOI":"10.1186\/1479-5876-10-85"},{"key":"2022031621185509000_i2590-017X-5-1-26-b16","doi-asserted-by":"crossref","unstructured":"Subbiah\n              V,\n            \n            \n              Puzanov\n              I,\n            \n            \n              Blay\n              JY,\n            \n            et al.\n          \n          Pan-cancer efficacy of vemurafenib in BRAF (V600)-mutant non-melanoma cancers.\n\t\t\t\t\tCancer Discov.\n\t\t\t\t\t2020;\n\t\t\t\t\t10:\n\t\t\t\t\t657\u2013\n\t\t\t\t\t663.","DOI":"10.1158\/2159-8290.CD-19-1265"},{"key":"2022031621185509000_i2590-017X-5-1-26-b17","doi-asserted-by":"crossref","unstructured":"Robertson\n              S,\n            \n            \n              Hyder\n              O,\n            \n            \n              Dodson\n              R,\n            \n            et al.\n          \n          The frequency of KRAS and BRAF mutations in intrahepatic 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with BRAF mutant intrahepatic cholangiocarcinoma-2 case reports and a brief review.\n\t\t\t\t\tJ Gastrointest Oncol.\n\t\t\t\t\t2016;\n\t\t\t\t\t7:\n\t\t\t\t\tE98\u2013\n\t\t\t\t\tE102.","DOI":"10.21037\/jgo.2016.09.13"},{"key":"2022031621185509000_i2590-017X-5-1-26-b20","doi-asserted-by":"crossref","unstructured":"Subbiah\n              V,\n            \n            \n              Lassen\n              U,\n            \n            \n              Elez\n              E,\n            \n            et al.\n          \n          Dabrafenib plus trametinib in patients with BRAF(V600E)-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial.\n\t\t\t\t\tLancet Oncol.\n\t\t\t\t\t2020;\n\t\t\t\t\t21:\n\t\t\t\t\t1234\u2013\n\t\t\t\t\t1243.","DOI":"10.1016\/S1470-2045(20)30321-1"},{"key":"2022031621185509000_i2590-017X-5-1-26-b21","doi-asserted-by":"crossref","unstructured":"Kocsis\n              J,\n            \n            \n              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