Expression levels of ROS1/ALK/c-MET and therapeutic efficacy of cetuximab plus chemotherapy in advanced biliary tract cancer

Nai Jung Chiang, Chiun Hsu, Jen Shi Chen, Hsiao Hui Tsou, Ying Ying Shen, Yee Chao, Ming Huang Chen, Ta Sen Yeh, Yan Shen Shan, Shiu Feng Huang, Li Tzong Chen

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6 Citations (Scopus)

Abstract

Aberrant expression of ROS1, ALK or c-MET (RAM) is implicated in carcinogenesis and cancer drug resistance. We retrospectively evaluated the effect of RAM expression on outcomes for advanced biliary tract cancer patients, who were treated with gemcitabine plus oxaliplatin (GEMOX), with or without cetuximab, in a randomized phase II trial. RAM expression levels on archived tissue sections were scored using immunohistochemistry (IHC). Of 110 tumors with IHC staining for all three markers, 18 were RAMhigh (IHC intensity 3+ for any markers). Ninety-two tumors were RAMlow (IHC intensity <3+ for all markers). All RAMhigh tumors were intra-hepatic cholangiocarcinomas (IHCC). Of the patients with IHCC (n = 80), median overall survival (OS) of RAMhigh group was inferior to that of the RAMlow group (5.7 vs. 11.7 months, p = 0.021). In multivariate analysis RAM high remained an independently adverse prognostic factor, with a hazard ratio of 2.01 (p = 0.039). In the RAM low group, GEMOX treatment with cetuximab significantly improved the disease control rate (68% vs. 41%, p = 0.044), median progression-free survival (7.3 vs. 4.9 months, p = 0.026), and marginally prolonged median OS (14.1 vs 9.6 months, p = 0.056), compared to GEMOX treatment alone. Future trials of anti-EGFR inhibitors for IHCC may consider RAM expression as a patient stratification factor.

Original languageEnglish
Article number25369
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 May 3

All Science Journal Classification (ASJC) codes

  • General

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