We have previously reported ctDNA profile in 246 patients (pts) with mUC derived from the LT (mLTUC) (Grivas et al ASCO GU 2017). mUC derived from the UT (mUTUC) is a clinically distinct entity with a more aggressive disease course. The ctDNA profile of mUTUC has not been previously characterized.
Data was obtained from pts with mUTUC who received ctDNA profiling as a part of routine clinical care using a CLIA-certified, CAP-accredited platform evaluating up to 70 genes. Genomic alterations (GAs) were pooled for the entire cohort. Comparison to the previously reported mLTUC was performed using the chi-square test.
Between Oct 2014 and Apr 2017, ctDNA results from 75 pts (M:F 30:45) with mUTUC were assessed. Median age of the cohort was 69 (range, 40-90). A median of 6.2 months had elapsed from the time of diagnosis with mUC and ctDNA assessment. Genomic alterations (GAs) were detected in 71 pts (95%), with an average/median of 4.5/3 GAs per pt (range, 0-35). Treatment related data was available in 30 pts (40%). The frequency of GAs in mUTUC vs mLTUC was as follows: TP53 (51% vs 52%), PIK3CA (20% vs 18%), ARID1A (16% vs 17%), EGFR (8% vs 13%), ERBB2 (8% vs 7%), FGFR3 (7% vs 11%), BRCA2 (6% vs 7%) and NF1 (6% vs 8%) (P=NS for all comparisons). Alteration types were diverse; for instance, FGFR3 alterations included fusion (FGFR3-TACC3 [n = 5]) and mutation (S249C [n = 3] and Y373C [n = 2]). Correlation of ctDNA profile with treatment and clinical outcome will be presented at the meeting.
Despite representing a clinically distinct entity, mUTUC demonstrated a ctDNA profile similar to that of mLTUC. These data may inform the design of clinical trials of targeted therapy (e.g., FGFR3 and ERBB2 inhibitors) in mUC, suggesting that inclusion of both mUTUC and mLTUC may be warranted.
Clinical trial identification
Legal entity responsible for the study
L.A. Kiedrowski: LAK is an employee of Guardant Health. R.J. Nagy: RJN is an employee of Guardant Health. K. Banks: KB is an employee of Guardant Health. R. Lanman: RL is an employee of Guardant Health. All other authors have declared no conflicts of interest.