(UroToday.com) In the on-demand poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Bellmunt provided an updated analysis from the DANUBE trial, evaluating PD-L1 as a predictor of survival in patients with metastatic urothelial carcinoma (mUC). The DANUBE trial was an open-label, phase III trial including patients with previously untreated mUC. The study did not meet its co-primary endpoints; however, numerically longer survival was observed in pts with high tumour PD-L1 expression who were treated with D or D+T compared with standard of care chemotherapy (SoC).
In the context of the DANUBE trial, patient tumour samples were stained with the VENTANA PD-L1 (SP263) assay and were prospectively scored on tumour cells (TCs) and immune cells (ICs) using thresholds of TC≥25%, IC≥25%, TC or IC≥25% (TC/IC25). Additionally, exploratory scoring of TC≥1%, combined positive score (CPS) ≥10, and ICs as a proportion of tumour area (ICTA) ≥5% was also performed on a subset of patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by unstratified log rank test according to these biomarker defined groups.
All of the PD-L1 algorithms, save for TC≥1% for D, improved the OS HR for of durvalumab or durvalumab plus tremelimumab vs SoC compared in the all-comers population.
Within treatment arms, using the TC/IC25 algorithm, survival was significantly longer in pts with high vs low PD-L1 expression who received either durvalumab plus tremelimumab (HR=0.71, p=0.0074) or durvalumab (HR=0.77, p=0.0324) but not SoC (HR=0.98, p=0.895). Both IC and TC PD-L1 expression contributed to patient selection.
Notably, the ability of PD-L1 to predict an OS benefit was impacted by subsequent therapy.
Presented by: Presented by: Joaquim Bellmunt, MD, PhD, Associate Professor, Medicine, Harvard Medical School, Director, Bladder Cancer Program, Beth Israel Deaconess Medical Center, Beth Israel, Boston, MA