title: Dramatic response to dabrafenib and trametinib combination in a BRAF V600E-mutated cholangiocarcinoma: implementation of a molecular tumour board and next-generation sequencing for personalized medicine.
abstract: This is the case of a 47-year-old woman diagnosed with chemotherapy and radiation-refractory BRAF V600E mutant, poorly differentiated intrahepatic cholangiocarcinoma (ICC), with multiple metastatic lesions within the liver, lungs, pleura, and bone, stage IV. Discussion of her malignancy's next-generation sequencing genomic information at a multidisciplinary molecular tumour board took place. The patient was considered a suitable candidate for dual BRAF and MEK inhibition, with the intent to prolong her survival and optimize the quality of life. We report her excellent tolerance and exceptional response to dual therapy with dabrafenib and trametinib, including symptomatic and sustained near-complete radiological improvement. We also briefly review the current knowledge of the genomics of cholangiocarcinoma with a focus on BRAF mutations, and make a point of the importance of the establishment of a molecular tumour board for personalized genomic medicine approaches. To our knowledge, this is the first reported case of the use of personalized genomic information for the successful management of a patient with ICC, and it is also the first description of dual BRAF and MEK targeted therapy in this malignancy, leading to what is considered an exceptional response.
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Perelman Center for Advanced Medicine, Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Loaiza-Bonilla
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Perelman Center for Advanced Medicine, Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Clayton
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Perelman Center for Advanced Medicine, Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Furth
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Perelman Center for Advanced Medicine, Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: O'Hara
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Perelman Center for Advanced Medicine, Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morrissette
keywords: BRAF; MEK; cholangiocarcinoma; dabrafenib; exceptional responder; genomic medicine; molecular tumour board; next-generation sequencing; personalized medicine; trametinib