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Published on: September 20, 2016
Spectrum of FGFR2/3 Alterations in Cell-Free DNA of Patients with Advanced Urothelial Carcinoma
Petros Grivas1, Lesli A Kiedrowski2, Guru P Sonpavde3
1University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, USA.
Abstract:
Detecting genomic alterations (GAs) in advanced urothelial carcinoma (aUC) can expand treatment options by identifying candidates for targeted therapies. Erdafitinib is FDA-approved for patients with platinum-refractory aUC with activating mutation or fusion in FGFR2/3. We explored the prevalence and spectrum of FGFR2/3 GAs identified with plasma cfDNA NGS testing (Guardant360) in 997 patients with aUC. FGFR2/3 GAs were detected in 201 patients (20%) with characterized activating GAs in 141 (14%). Our results indicate the Guardant360-based FGFR2/3 GA detection rate is similar to those described from previous studies employing tumor tissue testing, suggesting that plasma-based cfDNA NGS may non-invasively identify candidates for anti-FGFR targeted therapies.
Insights
Plasma NGS testing detected FGFR2/3 genomic alterations in 20% of advanced urothelial carcinoma patients. This non-invasive approach may identify candidates for targeted therapies like erdafitinib.
Area of Science:
- Oncology
- Genetics
- Molecular Diagnostics
Background:
- Genomic alterations (GAs) in advanced urothelial carcinoma (aUC) are crucial for identifying patients eligible for targeted therapies.
- Erdafitinib is an FDA-approved targeted therapy for platinum-refractory aUC with specific FGFR2/3 alterations.
Purpose of the Study:
- To determine the prevalence and spectrum of FGFR2/3 GAs in aUC using plasma cell-free DNA (cfDNA) next-generation sequencing (NGS).
- To evaluate the utility of Guardant360 plasma NGS for identifying patients who could benefit from anti-FGFR targeted therapies.
Main Methods:
- Plasma cfDNA NGS (Guardant360) was performed on 997 patients with aUC.
- Analysis focused on the detection and characterization of FGFR2/3 GAs.
Main Results:
- FGFR2/3 GAs were detected in 201 out of 997 patients (20%).
- Activating FGFR2/3 GAs were identified in 141 patients (14%).
- The detection rate of FGFR2/3 GAs using plasma cfDNA NGS was comparable to previous studies using tumor tissue testing.
Conclusions:
- Plasma cfDNA NGS is a viable non-invasive method for detecting FGFR2/3 GAs in aUC.
- This approach can effectively identify patients suitable for FGFR-targeted therapies, potentially expanding treatment options.
