Fgfr2/3 Genomic Alterations (Ga) In Cell-Free (Cf)Dna From Patients (Pts) With Advanced Urothelial Carcinoma (Auc)

565 Background: Erdafitinib is approved in pts with aUC with relevant FGFR2/3 GA. BLC2001 trials in pts with activating FGFR2/3 mutations reported 40% ORR to erdafitinib (49% for those with single nucleotide variants [SNVs] and 16% with fusions), 39% stable disease rate, and potentially reduced response to anti-PD-L1. Genomic profiling with plasma cfDNA next-generation sequencing (NGS) is increasingly used to identify targetable GA in pts with advanced solid tumors and presents a minimally invasive option for identification of FGFR2/3 GA. Methods: Genomic data from the Guardant360 database were queried from clinical results released from 10/19/15 - 8/28/19 for clinical samples submitted with diagnoses of aUC or related diagnoses (e.g. bladder cancer, renal pelvis carcinoma). All assays included FGFR2/3 fusions and complete sequencing of all critical exons harboring sensitizing FGFR2/3 SNVs. Results: 1349 results from 1096 unique pts were identified. Somatic GA were identified in 1192 tests (88%) from 997 pts. Fusions and/or nonsynonymous SNVs in FGFR2/3 were identified in 201 pts (20%); 141 pts (14%) had at least one characterized activating FGFR2/3 GA. Of 34 pts (3.4%) with FGFR3 fusions, partners included TACC3 (32), JAKMIP1 (1), and TNIP2 (1). Overall, most SNVs identified in FGFR3 were predicted to be activating (103/125, 82%) whereas in FGFR2 most were variants of uncertain significance (VUS; 62/72, 86%). Of 89 unique variants (59 in FGFR2, 30 in FGFR3), 19 (21%) were activating mutations (7 in FGFR2, 12 in FGFR3). The most common activating SNVs in FGFR3 were S249C (58 pts), Y373C (20) and R248C (10), and in FGFR2 was N549K (4). VUS in both genes were individually uncommon (no VUS recurring in >3 pts). Median copy number-adjusted clonality of SNVs in FGFR3 was higher than those in FGFR2 (0.80 vs 0.20); this remained true when limiting to only characterized activating mutations (0.84 vs 0.17). Conclusions: cfDNA NGS analysis identifies fusions and a broad spectrum of SNVs in FGFR2/3, including heterogeneous subclonal mutations, at a rate similar to reported tissue testing. cfDNA is a minimally invasive option for pts with aUC to assess candidacy for erdafitinib and clinical trials.