Frequency and clinicopathological characteristics of biliary tract carcinomas harboring the FGFR2-fusion gene: A prospective observational study (PRELUDE study)

Abstract

Background: Patients with biliary tract carcinomas (BTC) have a dismal prognosis. The FGFR2-fusion gene has been recently implicated in 14-17% of intrahepatic cholangiocarcinomas (ICC) and is expected to be a promising novel druggable target. However, the exact frequency in patients of advanced BTC (including cancers other than ICC) and detailed clinicopathological background of the FGFR2-fusion have not been sufficiently elucidated. Methods: Histologically confirmed advanced or recurrent BTC patients who planned to or received systemic chemotherapy were eligible. Because FGFR2-fusion gene was identified in only ICC and perihilar cholangiocarcinoma (PCC) among first 209 patients (March 2014 to February 2016), we limited the subjects to those with ICC/ PCC and continued enrollments until November 2018. To determine FGFR2-fusion status, break-apart fluorescent in situ hybridization and target RNA sequencing were performed on formalin fixed, paraffin-embedded tumor samples obtained by resection or core biopsy. Results: During the entire study period, 445 patients were registered and 423patients (272 ICC, 83 PCC, 20 distal cholangiocarcinoma, 43 carcinoma of gallbladder, and 5 ampullary carcinoma) were successfully tested for FGFR2-fusion status. Among those, 21 ICC and 4 PCC patients were identified as harboring the FGFR2-fusion. Characteristics of FGFR2-fusion positive patients were as follows: male/female = 19/6; median age (range) = 60 (41-76); stage (metastatic/locally advanced/recurrent) = 15/ 2/8. Macroscopic type was mass forming type in all 21 ICC patients. Age of<65 (0.032), consumption of>60g of ethanol/day (p=0.023), and HCV Ab and/or HBs Ag positive (p=0.012) were significantly related with FGFR2-fusion positive status (logistic regression). Conclusions: In this study, frequency of FGFR2-fusion was 7.7%in advanced ICC patients, which was lesser than the previous reports. We found that 4.8% of the PCC patients also harbored the FGFR2-fusion. Younger age, alcohol abuse, and hepatitis B or C positive status were related to FGFR2-fusion positive status. The survival data of FGFR2-fusion positive patients will be presented at the meeting.