@article{c46eb97ca2644b3f858ae303cfc1cf0e,
title = "Randomised phase II trial (SWOG S1310) of single agent MEK inhibitor trametinib Versus 5-fluorouracil or capecitabine in refractory advanced biliary cancer",
abstract = "Background: The rationale for the evaluation of trametinib in advanced biliary cancer (BC) is based on the presence of mitogen-activated protein kinase alterations and on earlier promising results with MEK inhibitors in BC. Methods: Patients with histologically proven BC who progressed on gemcitabine/platinum were randomised to trametinib daily (arm 1) versus fluoropyrimidine therapy (infusional 5-fluorouracil or oral capecitabine, arm 2). The primary end-point was overall survival (OS). Secondary end-points included progression free survival (PFS) and response rate. A planned interim futility analysis of objective response was performed on the first 14 patients registered to the trametinib arm. Results: The study was stopped early based on the lack of measurable response in the trametinib arm. A total of 44 eligible patients were randomised (24 patients in arm 1 and 20 patients in arm 2). Median age was 62 years and the primary sites of tumour were cholangiocarcinoma (68%) and gallbladder (32%). The overall response rate was 8% (95% CI 0%–19%) in arm 1 versus 10% (95% CI 0%–23%) in arm 2 (p > .99) Median OS was 4.3 months for arm 1 and 6.6 months for arm 2. The median PFS was 1.4 months for arm 1 and 3.3 months for arm 2. Conclusions: This is the first prospective randomised study of a targeted agent versus chemotherapy for the second-line treatment of BC. In this unselected population, the interim analysis result of unlikely benefit with trametinib resulted in early closure.",
keywords = "5-Fluorouracil, Advanced biliary cancer, Capecitabine, MEK inhibitor",
author = "Kim, {Richard D.} and Shannon McDonough and El-Khoueiry, {Anthony B.} and Bekaii-Saab, {Tanios S.} and Stein, {Stacey M.} and Vaibhav Sahai and Keogh, {George P.} and Kim, {Edward J.} and Baron, {Ari D.} and Siegel, {Abby B.} and Afsaneh Barzi and Guthrie, {Katherine A.} and Milind Javle and Howard Hochster",
note = "Funding Information: This work was funded by National Institutes of Health, National Cancer Institute grant awards CA180888, CA180819, CA180826, CA189858, CA180801, CA180846, CA189954, CA189821, CA180850, CA189960, CA46368, CA189830, CA46282, CA11083, CA189971, CA189972, CA180818, CA180818, CA189872, CA180798, CA180835, CA46113, CA58723, CA12644, CA180830; and in part by GlaxoSmithKline (Novartis Pharmaceuticals Corporation). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.RK has received honoraria from Bayer, Bristol Myer Squib (BMS) and Lilly for consulting; research funding from Bayer, BMS and Eisai. AE has received honoraria from BMS, Bayer, Merck, Eisai, Exelixis, Genentech/Roche, Astra Zeneca, Astex, Agenus, Novartis, EMD serono and Cytomx for consulting/advisory role; research funding from Astra Zeneca and Astex. TB has received honoraria from AbbVie, Bayer, Genentech, Glenmark, Imugene and Immuneering for consulting. SMS has received honoraria from Merck, BMS, Genentech and Eisai for advisory boards. VS has received honoraria from Celegene, Ipsen and Halozyme for consulting; research funding from Celgenem BMS, Halozyme and Medimmune. EK has received honoraria from Vicus, Armo, Bluepath Solutions and Guidepoint for advisory board and consulting; speaker fee from Guardant Health; research funding from BMS, Sanumed, Boston Biomedical, Halozyme, Merck, Celegene, Oncomed, EpicentRx and Astellas Pharma. ADB has received fees from BMS, Eli Lilly and Amgen for speaker's bureau. AS currently is a full-time employee of Merck since August 2015. Funding Information: This work was funded by National Institutes of Health , National Cancer Institute grant awards CA180888, CA180819, CA180826, CA189858, CA180801, CA180846, CA189954, CA189821, CA180850, CA189960, CA46368, CA189830, CA46282, CA11083, CA189971, CA189972, CA180818, CA180818, CA189872, CA180798, CA180835, CA46113, CA58723, CA12644, CA180830; and in part by GlaxoSmithKline (Novartis Pharmaceuticals Corporation). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2020",
month = may,
doi = "10.1016/j.ejca.2020.01.026",
language = "English (US)",
volume = "130",
pages = "219--227",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}