Abstract 2276
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.
Clinical trial identification
UMIN000014767.
Editorial acknowledgement
Legal entity responsible for the study
National Cancer Center.
Funding
National Cancer Center Research and Development Fund.
Disclosure
M. Ikeda: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer Yakuhin; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Yakult; Advisory / Consultancy: Otsuka Pharmaceutical; Advisory / Consultancy: Daiichi-Sankyo; Honoraria (self): Sumitomo Dainippon Pharma; Honoraria (self), Advisory / Consultancy: Teijin Pharma; Honoraria (self): EA Pharma; Honoraria (self): Kaken Pharmaceutical; Advisory / Consultancy: Shire; Honoraria (self): MSD; Advisory / Consultancy, Research grant / Funding (institution): ASLAN Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharmaceutical; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Nano Carrier; Honoraria (institution): Gilead; Advisory / Consultancy: Astellas Pharma; Research grant / Funding (institution): Takeda Pharmaceutical; Research grant / Funding (institution): J-Pharma; Advisory / Consultancy: Micron. M. Ueno: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Yakult Honsha; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): Teijin Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Shire; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): MSD; Research grant / Funding (institution): NanoCarrier; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Aslan Pharmaceuticals. T. Ioka: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho; Honoraria (self): Yakult Honsha; Honoraria (self): Chugai; Honoraria (self), Advisory / Consultancy: Daiichi-Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Shire Japan; Honoraria (self), Advisory / Consultancy: Otsuka; Research grant / Funding (institution): Dainippon Sumitomo; Research grant / Funding (institution): Takara-bio; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Nihon Zouki. A. Naganuma: Speaker Bureau / Expert testimony: AbbVie; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Gilead; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Novartis. Y. Nakai: Honoraria (self), Research grant / Funding (self): Taiho Pharmaceutical; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Research grant / Funding (self): Eisai; Research grant / Funding (self): Yakult Honsha; Research grant / Funding (self): J-Pharma. M. Kanai: Licensing / Royalties: Therabiopharma Ltd; Licensing / Royalties: JMS Co., Ltd. S. Shimizu: Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Baxalta Japan; Research grant / Funding (institution): Taiho pharmaceutical; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Yakult; Research grant / Funding (institution): IQVIA Survices Japan. T. Yamanaka: Honoraria (self): Pfizer. T. Shibata: Advisory / Consultancy: MSD. C. Morizane: Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): Lilly; Honoraria (self), Research grant / Funding (institution): Nobelpharma; Honoraria (self): Fujifilm; Honoraria (self): Teijin Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Yakult Honsha; Honoraria (self): AbbVie; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): J-Pharma. T. Okusaka: Honoraria (self), Research grant / Funding (institution): Novartis Pharma KK; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self), Research grant / Funding (institution): Bayer Yakuhin; Honoraria (self): Nobel Pharma; Honoraria (self), Research grant / Funding (institution): Yakult; Honoraria (self): FUJIFILM; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self): EA pharma; Honoraria (self), Research grant / Funding (institution): Eisai; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Teijin; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self): Shire; Honoraria (self): Takara Bio; Honoraria (self): AbbVie; Honoraria (self): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Dainippon Sumitomo; Advisory / Consultancy: Zeria; Advisory / Consultancy, Research grant / Funding (institution): Bristol Myers; Research grant / Funding (institution): Kowa; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Chugai. All other authors have declared no conflicts of interest.
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