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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
FGFR2-fusions define a clinically actionable molecular subset of pancreatic cancer
Leah Stein1,2, Karthikeyan Murugesan3, Julie W Reeser1
1Comprehensive Cancer Center and James Cancer Hospital, The Ohio State University, Columbus, OH, USA.
Abstract:
Genomic alterations in fibroblast growth factor receptor (FGFR) genes are present in a small number of metastatic pancreatic ductal adenocarcinomas (PDAC) and may represent an emerging subgroup of patients likely to benefit from FGFR targeted therapies. Here we present four FGFR2 fusion-positive metastatic PDAC patients who exhibited durable responses or disease control to FGFR kinase inhibitors. Utilizing our custom FGFR focused cell-free DNA assay, FGFR-Dx, we serially monitored variant allele fractions of FGFR2 fusions during FGFR inhibitor treatment and observed dynamic changes correlating with clinical responses. Genomic analysis of 30,229 comprehensively profiled pancreatic cancers revealed FGFR1-3 fusions in 245 cases, an incidence of 0.81%. FGFR fusions were generally mutually exclusive from other known oncogenes. Our findings provide clinical evidence for identifying and treating FGFR2 fusion-positive PDAC patients with FGFR targeted therapy.
Insights
Fibroblast growth factor receptor (FGFR) fusions are found in metastatic pancreatic cancer and may respond to targeted therapies. This study shows FGFR2 fusions in PDAC patients benefit from FGFR inhibitors, with monitoring via cell-free DNA assays.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Genomic alterations in fibroblast growth factor receptor (FGFR) genes are identified in a subset of metastatic pancreatic ductal adenocarcinomas (PDAC).
- These alterations may indicate a patient subgroup that could benefit from FGFR-targeted therapies.
Purpose of the Study:
- To present clinical evidence of FGFR2 fusions in metastatic PDAC.
- To evaluate the efficacy of FGFR kinase inhibitors in patients with FGFR2 fusions.
- To assess the utility of cell-free DNA (cfDNA) assays for monitoring treatment response.
Main Methods:
- Case study of four patients with FGFR2 fusion-positive metastatic PDAC treated with FGFR inhibitors.
- Serial monitoring of FGFR2 fusion variant allele fractions using a custom FGFR-focused cfDNA assay (FGFR-Dx).
- Genomic analysis of 30,229 pancreatic cancer cases to determine the incidence of FGFR1-3 fusions.
Main Results:
- Four patients with FGFR2 fusion-positive metastatic PDAC showed durable responses or disease control with FGFR inhibitors.
- Dynamic changes in FGFR2 fusion cfDNA levels correlated with clinical responses during treatment.
- FGFR1-3 fusions were identified in 0.81% (245/30,229) of pancreatic cancers and were generally mutually exclusive from other known oncogenes.
Conclusions:
- FGFR2 fusions represent a targetable subset of metastatic PDAC.
- FGFR kinase inhibitors demonstrate clinical efficacy in patients with FGFR2 fusion-positive PDAC.
- The FGFR-Dx assay is a valuable tool for monitoring treatment response in these patients.
