160282-173

Next Generation Sequencing (NGS) to reveal mutations in IDH1 and its effect on patient (pt) outcomes in advanced biliary tract cancer (aBTC) who received gemcitabine and cisplatin (GC).

Subcategory: 
Category: 
Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 

287

Poster Board Number: 
Poster Session B Board #E11
Citation: 
J Clin Oncol 34, 2016 (suppl 4S; abstr 287)
Author(s): 
Daniel H. Ahn, Chul Ahn, Apurva Jain, Sameh Mikhail, Christina Sing-Ying Wu, Richard M. Goldberg, Kristen Keon Ciombor, Anne M. Noonan, Priyanka Sadavartia, Rachna T. Shroff, Milind M. Javle, James Lin Chen, Tanios S. Bekaii-Saab; The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Richard J. Solove Research Institute, Columbus, OH; The University of Texas Southwestern Medical Center, Dallas, TX; The University of Texas MD Anderson Cancer Center, Houston, TX; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital, Solove Research Institute, Columbus, OH; The Ohio State University Wexner Medical Center, Columbus, OH; The Ohio State University, James Cancer Hospital, Columbus, OH; The Ohio State University, Columbus, OH; The Ohio State University Comprehensive Cancer Center, Columbus, OH

Abstract Disclosures

Abstract: 

Background: aBTC is uncommon and has a dismal prognosis with limited therapeutic options. First-line therapy for untreated aBTC is GC, with no approved therapies in the refractory setting. To assess for tumor-specific genetic variants that affect outcomes in patients (pts) who received GC in aBTC, we performed NGS in pts treated with who received GC as first-line therapy. Methods: Archival formalin-fixed, paraffin-embedded samples from pts with mBTC from Ohio State University and MD Anderson Cancer Center who received GC in the first-line and underwent NGS as part of routine care. 315 cancer-related genes plus select introns from 28 genes altered in solid tumors were included in the NGS panel. Univariate Cox regression model was used to determine the association between gene mutations with progression free survival (PFS) and (OS). Results: 80 evaluable pts with aBTC treated with first-line GC chemotherapy underwent successful genomic profiling. A total of 414 cancer-specific mutations were identified, where 49 (12%) genes had mutations with > 5% frequency. 17 of the 49 were known mutations. From the comprehensive analysis, somatic mutations in IDH1 (11 of 80 pts; 13%) (HR 0.31; p = 0.035) was associated with improved overall survival (OS) and progression free survival (PFS). Pts wild type for IDH1 had a median OS of 17.7 months and PFS of 4.5 months, while those with an IDH1 mutation had a median OS that was not reached and an improved PFS of 5.7 months. Conclusions: Somatic mutations in IDH1 were associated with improved clinical outcomes in pts with aBTC who received GC as first-line therapy which is consistent with other solid tumor malignancies. IDH1 is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive utility and its relevance in pt outcomes in aBTC.