Randomised phase II trial (SWOG S1310) of single agent MEK inhibitor trametinib Versus 5-fluorouracil or capecitabine in refractory advanced biliary cancer

Richard D. Kim, Shannon McDonough, Anthony B. El-Khoueiry, Tanios S. Bekaii-Saab, Stacey M. Stein, Vaibhav Sahai, George P. Keogh, Edward J. Kim, Ari D. Baron, Abby B. Siegel, Afsaneh Barzi, Katherine A. Guthrie, Milind Javle, Howard Hochster

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalEuropean Journal of Cancer
Volume130
DOIs
StatePublished - May 2020

Keywords

  • 5-Fluorouracil
  • Advanced biliary cancer
  • Capecitabine
  • MEK inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kim, R. D., McDonough, S., El-Khoueiry, A. B., Bekaii-Saab, T. S., Stein, S. M., Sahai, V., Keogh, G. P., Kim, E. J., Baron, A. D., Siegel, A. B., Barzi, A., Guthrie, K. A., Javle, M., & Hochster, H. (2020). Randomised phase II trial (SWOG S1310) of single agent MEK inhibitor trametinib Versus 5-fluorouracil or capecitabine in refractory advanced biliary cancer. European Journal of Cancer, 130, 219-227. https://doi.org/10.1016/j.ejca.2020.01.026