<div>AbstractPurpose:<p>This retrospective analysis of the largest available clinico-genomic database used de-identified patient-level electronic health record–derived real-world data (RWD) combined with FoundationOne comprehensive genomic profiling (CGP) to characterize patients with metastatic urothelial carcinoma (mUC) treated in the real-world setting, detect potential biomarkers, and develop a bladder immune performance index (BIPI).</p>Experimental Design:<p>Patients with mUC who started front-line single-agent immune checkpoint inhibitors (ICI) and an unmatched group treated with front-line platinum-based chemotherapy between January 1, 2011, and September 30, 2019, were selected. Clinical and genomic data were correlated with overall survival (OS). A novel BIPI predicting outcome with ICIs was developed using machine learning methods and validated using data from a phase II trial (NCT02951767).</p>Results:<p>In ICI-treated patients (<i>n</i> = 118), high tumor mutational burden (≥10 mutations/megabase) was associated with improved OS (HR, 0.58; 95% CI, 0.35–0.95; <i>P</i> = 0.03). In chemotherapy-treated patients (<i>n</i> = 268), those with high APOBEC mutational signature had worse OS (HR, 1.43; 95% CI, 1.06–1.94; <i>P</i> = 0.02). Neither <i>FGFR3</i> mutations nor DNA damage–repair pathway alterations were associated with OS. A novel BIPI combining clinical and genomic variables (nonmetastatic at initial diagnosis, normal or above normal albumin level at baseline, prior surgery for organ-confined disease, high tumor mutational burden) identified ICI-treated patients with longest OS and was validated in an independent dataset.</p>Conclusions:<p>Contemporary RWD including FoundationOne CGP can be used to characterize outcomes in real-world patients according to biomarkers beyond PD-L1. A validated, novel clinico-genomic BIPI demonstrated satisfactory prognostic performance for OS in patients with mUC receiving front-line ICI therapy.</p></div>

<div>AbstractPurpose:<p>This retrospective analysis of the largest available clinico-genomic database used de-identified patient-level electronic health record–derived real-world data (RWD) combined with FoundationOne comprehensive genomic profiling (CGP) to characterize patients with metastatic urothelial carcinoma (mUC) treated in the real-world setting, detect potential biomarkers, and develop a bladder immune performance index (BIPI).</p>Experimental Design:<p>Patients with mUC who started front-line single-agent immune checkpoint inhibitors (ICI) and an unmatched group treated with front-line platinum-based chemotherapy between January 1, 2011, and September 30, 2019, were selected. Clinical and genomic data were correlated with overall survival (OS). A novel BIPI predicting outcome with ICIs was developed using machine learning methods and validated using data from a phase II trial (NCT02951767).</p>Results:<p>In ICI-treated patients (<i>n</i> = 118), high tumor mutational burden (≥10 mutations/megabase) was associated with improved OS (HR, 0.58; 95% CI, 0.35–0.95; <i>P</i> = 0.03). In chemotherapy-treated patients (<i>n</i> = 268), those with high APOBEC mutational signature had worse OS (HR, 1.43; 95% CI, 1.06–1.94; <i>P</i> = 0.02). Neither <i>FGFR3</i> mutations nor DNA damage–repair pathway alterations were associated with OS. A novel BIPI combining clinical and genomic variables (nonmetastatic at initial diagnosis, normal or above normal albumin level at baseline, prior surgery for organ-confined disease, high tumor mutational burden) identified ICI-treated patients with longest OS and was validated in an independent dataset.</p>Conclusions:<p>Contemporary RWD including FoundationOne CGP can be used to characterize outcomes in real-world patients according to biomarkers beyond PD-L1. A validated, novel clinico-genomic BIPI demonstrated satisfactory prognostic performance for OS in patients with mUC receiving front-line ICI therapy.</p></div>

Supplementary Figure from Clinico-Genomic Characterization of Patients with Metastatic Urothelial Carcinoma in Real-World Practice Identifies a Novel Bladder Immune Performance Index (BIPI)

Supplementary Figure from Clinico-Genomic Characterization of Patients with Metastatic Urothelial Carcinoma in Real-World Practice Identifies a Novel Bladder Immune Performance Index (BIPI)

Supplementary Figure from Clinico-Genomic Characterization of Patients with Metastatic Urothelial Carcinoma in Real-World Practice Identifies a Novel Bladder Immune Performance Index (BIPI)