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).
Patients with mUC who started front-line single-agent immune checkpoint inhibitors (ICIs) 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).
In ICI-treated patients (n=118), high tumor mutational burden (≥10 mutations/megabase) was associated with improved OS (HR 0.58 [95% CI, 0.35-0.95]; P=0.03). In chemotherapy-treated patients (n=268), those with high APOBEC mutational signature had worse OS (HR 1.43 [95% CI, 1.06-1.94]; P=0.02). Neither FGFR3 mutations nor DNA damage-repair pathway alterations were associated with OS. A novel BIPI combining clinical and genomic variables (non-metastatic at initial diagnosis, normal or above normal albumin level at baseline, prior surgery for organ-confined disease, high TMB) identified ICI-treated patients with longest OS and was validated in an independent dataset.
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Jul 25 [Epub ahead of print]
Bernadett Szabados, Mariano Ponz-Sarvis, Robson Machado, Diego Saldana, Edward E Kadel, Romain Banchereau, Fanny Bouquet, Marius Garmhausen, Thomas Powles, Carsten Schr der
Barts Cancer Institute, Queen Mary University of London and University College London Hospital, London, United Kingdom., Clinica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain., F. Hoffmann-La Roche Ltd, Switzerland., Genentech, South San Francisco, CA, United States., Institut Roche, Boulogne-Billancourt, France., Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust, London, United Kingdom., F. Hoffmann-La Roche Ltd, Basel, Switzerland.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35877091