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- Title
Circulating tumor DNA molecular analyses and real-world evidence outcomes of FGFR2 amplified gastroesophageal cancers.
- Authors
Shariff, Bushra; Barnett, Reagan M; Dayyani, Farshid; Maron, Steven B; Mcgriskin, Rory; Klempner, Samuel; Donderici, Elifnur Yay; Zhang, Nicole; Masannat, Jude; Drusbosky, Leylah M; Mehta, Rutika
- Abstract
Purpose In addition to the existing biomarkers HER2 and PD-L1, FGFR2b has become an area of interest for the development of new targeted-based treatment. Given that clinical evaluation of FGFR2 targeted therapy is underway, we sought to elucidate the genomic landscape of FGFR2 amp in gastroesophageal cancer (GEC) using a circulating tumor DNA (ctDNA) platform. Materials and Methods We retrospectively evaluated the Guardant Health database from 2017 to 2022 for patients with GECs with Guardant360 ctDNA next-generation sequencing (NGS) performed. We assessed co-occurring genetic alterations for patients who harbored FGFR2 amp versus FGFR2 null. We also explored real-world evidence database with Guardant Health, publicly available genomic databases (MSK cohort using cBioPortal), and pooled clinical data from large-volume cancer centers for FGFR2 amp GECs. Results Less than 4% of patients with GEC in the Guardant Health database were identified to be FGFR2 amp. The most commonly co-occurring gene mutations were TP53 , CTNNB1 , CDH1 , and RHOA. Upon interrogation of the MSK cohort, these same genes were not significant on tissue NGS in the FGFR2 amp cohort of GEC. In the pooled institutional cohort, we noted that FGFR2 amp tumors were most commonly involving the gastroesophageal junction (GEJ). The overall survival of these patients was noted at 13.1 months. Conclusion FGFR2 is a validated target in GECs, and the contexture of FGFR2 amp will be important in defining patient subgroups with responses to FGFR2-directed therapy. Using ctDNA to provide a more detailed genomic landscape in patients with GECs will allow the advancement of targeted therapy in the near future for these aggressive cancers.
- Subjects
MITOGEN-activated protein kinases; STOMACH tumors; GENOMICS; IMMUNOTHERAPY; ESOPHAGEAL tumors; TUMOR markers; RETROSPECTIVE studies; BODY fluid examination; NUCLEIC acids; EXTRACELLULAR space; GENETIC mutation; CELL receptors; OVERALL survival; SEQUENCE analysis
- Publication
Oncologist, 2024, Vol 29, Issue 8, p672
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyae061