Abstract 3395: Clinical impact of FGFR inhibitors on FGFR2 positive pancreatic cancer
Authors: Stein Leah , Reeser Julie W. , Wing Michele R. , Murugesan Karthikeyan , Paruchuri Anoosha , Risch Zachary , Samorodnitsky Eric , Hoskins Emily L. , Smith Amy , Dao Thuy , Babcook Melissa , Imam Muhammad , Freud Aharon , Roychowdhury Sameek 
Published: April 2023

Abstract
Objectives: Here we describe the durable clinical outcomes of four FGFR2 fusion positive pancreatic cancer patients treated with FGFR inhibitors as well as a pancreatic specific analysis of FGFR alterations through our collaboration with Foundation Medicine, Inc. (FMI).
Methods: We identified four patients with FGFR2 fusion positive metastatic pancreatic cancer through tumor RNAseq (OSU-SpARKFuse) which identifies gene fusions from cell free DNA (cfDNA). We assessed two tumor markers (Ca19-9 and FGFRDx, an FGFR-focused cell free DNA liquid biopsy assay) and various clinical outcomes (Best overall response, duration, and side effects to their treatments). Additionally, 10,146 tumor-tissue clinical cases of pancreatic cancers were assayed by hybrid-capture based comprehensive genomic profiling (Foundation Medicine, Inc.) to identify genomic alterations in &gt;300 cancer-associated genes, MSI, and tumor mutation burden (TMB).
Results: All four patients demonstrated durable clinical responses to various FGFR inhibitors. Patient 1 harbored an FGFR2-USP33 fusion and exhibited a partial response to pemigatinib for 25 months following progression on gemcitabine/abraxane and FOLFIRI chemotherapy. Patient 2 harbored an FGFR2-INA fusion with 12 months of stable disease to pazopanib after experiencing progression from chemotherapy. Patient 3 harbored an FGFR2-INA fusion and exhibited a 12+ month on-going, partial response to pemigatinib. Patient 4 harbored an FGFR2-CEP55 fusion and demonstrated stable disease on ponatinib for 15 months, a 24-month response to gemcitabine/platinum chemotherapy, and a 7+ month on-going partial response to infigratinib.  Through the genomic profiling of 10,146 tumor-tissue clinical cases of pancreatic cancer, we identified 108 FGFR fusions resulting in a prevalence of 1%. We are currently investigating co-occurring and mutually-exclusive genomic alterations, including TMB and MSI-H status, for pancreatic cancer patients harboring FGFR alterations.
Conclusions: This retrospective analysis provides clinical evidence that there is a subpopulation of KRAS wild-type FGFR2 fusion positive pancreatic patients who can have beneficial and lasting responses to FGFR inhibitors further suggesting a need to investigate and expand the availability of FGFR inhibitors to more cancer types.
Citation Format: Leah Stein, Julie W. Reeser, Michele R. Wing, Karthikeyan Murugesan, Anoosha Paruchuri, Zachary Risch, Eric Samorodnitsky, Emily L. Hoskins, Amy Smith, Thuy Dao, Melissa Babcook, Muhammad Imam, Aharon Freud, Sameek Roychowdhury. Clinical impact of FGFR inhibitors on FGFR2 positive pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3395.