title: Impressive response to dualBRAFand MEK inhibition in patients with BRAF mutant intrahepatic cholangiocarcinoma-2 case reports and a brief review.
abstract: Intrahepatic cholangiocarcinoma (ICC) typically presents at an advanced stage and is associated with a poor oncological outcome. The median survival for metastatic ICC is less than 1 year with standard chemotherapy. ICC is associated with distinct oncogenic drivers includingIDH(isocitrate dehydrogenase),HER-2(human epidermal growth factor 2), andBRAF(v-Raf murine sarcoma viral oncogene homolog B), which may benefit from matching targeted therapies. Hereby we report 2 cases ofBRAFV600E refractory ICC treated with dualBRAFand MEK inhibitors (dabrafenib and trametinib) with excellent clinical and radiological response to therapy and with protracted duration of disease control. Our first patient achieved CR (complete remission) at 6 months of treatment with ultimate disease progression at 9 months. The second patient achieved a PR (partial response) at 2 months from starting treatment and remains progression free at 5 months. Our results confirm the activity of dualBRAFand MEK targeting inBRAFmutated ICC, adding further support to 3 additional case-reports in the literature. Dual targeting appears superior to other case reports with BRAF inhibition alone and appear favorable to historic data with cytotoxic chemotherapy. Given the poor outlook and refractoriness ofBRAFmutant ICC, future studies should focus on early integration of BRAF/MEK inhibition.
authors.affiliation: Department of Medicine, Apollo Cancer Hospital, Jubilee Hills, Hyderabad, India.
authors.forename: Viraj
authors.initials: V
authors.lastname: Lavingia
authors.affiliation: Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Fakih
keywords: BRAF; Intrahepatic cholangiocarcinoma (ICC); MEK; dabrafenib; trametinib