Response to platinum-based therapy (PBT) and immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC) patients (pts) with genomic alterations (GA) in homologous recombination repair (HRR) genes.

447Background: Deleterious GA in genes of the HRR pathway and tumor mutational load (TML; mutations/Mb) were shown to predict response to PBT and ICI; further validation can be informative. We assessed the predictive role of such GA in mUC. Methods: Tissue from mUC pts treated with PBT or ICI in the 1st line setting underwent genomic profiling (GP) via FoundationOne. Pts were analyzed in 2 groups based on the presence of potentially function-impairing GA (using classification criteria) in any of 15 pre-selected HRR genes. Exploratory assessment of overall response rate (ORR; RECIST v1.1), progression-free and overall survival (PFS, OS) based on presence of relevant GA was performed using Cox proportional hazards model, Kaplan Meier estimates, and Fisher’s exact test. Results: GA were noted in 22% of 88 identified mUC pts with available GP from 2012 to 2017. The most common deleterious GA were BRCA1/2 (n=6), ATM (n=6), CDK12 (n=2), BRIP1 (n=2), BARD1 (n=1), RAD51 (n=1), and CHEK2 (n=1). Of 88 pts, 62 were ...