930P - Comparison of immuno-oncology (IO) biomarkers in adenocarcinoma (ACB), urothelial carcinoma (UCB) and squamous cell carcinoma (SCCB) of the bladder, with interim results from PURE01

Abstract

BackgroundUsing comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) we compared the frequency of IO biomarkers in ACB, UBC and SCCB. We also report the interim results of neoadjuvant pembrolizumab in patients (pts) with muscle-invasive bladder cancer (MIBC) and variant histologies from PURE01 (NCT02736266). MethodsWithin FMI database, 143 cases of ACB, 2,142 cases of UCB and 83 cases of SCCB were subjected to CGP using a hybrid-capture based assay. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC using the Ventana SP-142 assay with >1% tumor cell or immunocyte (TILs) scoring positive. Among 96 pts of PURE01, 15 had predominant variant SCCB histology. ResultsACB patients were younger and more often female than UBC and SCCB (P<0.0001). UBC and SCCB had a higher genomic alterations per tumor (GA/tumor) than ACB (P=0.01). The UBC and SCCB had a significantly higher TMB than ACB (P<0.0001) including mean TMB and TMB >/= 20 mut/Mb (P<0.0001). CD274(PD-L1) was amplified more frequently in SCCB than ACB or UBC (P<0.0001). MSI high status was very uncommon in all tumor types. The frequencies of PD-L1 expression in both tumor cells and TILs was higher in UBC and SCCB than in ACB (P<0.0001). In PURE01, 5 SCCB (33.3%) achieved pT0 response, and 10 (66.7%) a pT<2 response.Table930PTableAdenocarcinoma (ACB)Urothelial Carcinoma (UBC)Squamous Cell Carcinoma (SCCB)Cases1432,14283Median Age (Range) In years58 (24-83)67 (19-88)62 (31-88)Males/Females57/861597/54545/38GA/tumor5.47.78.2MSI High2/106 (2%)11/1661 (1%)1/69 (1%)CD274 (PD-L1) gene amplification0 (0%)17 (1%)4 (5%)Mean TMB2.4 mut/Mb9.9 mut/Mb10.4 mut/MbTMB >/= 10 mut/Mb14 (10%)697 (32%)26 (31%)TMB >/= 20 mut/Mb4 (3%)243 (11%)13 (16%)PD-L1 IHC Positive Tumor Cells2/11 (18%)76/244 (31%)3/10 (30%)PD-L1 IHC Positive TILs0/11 (0%)74/244 (29%)3/10 (30%) ConclusionsDeep sequencing reveals significant differences in IO biomarkers among the 3 major types of bladder carcinomas. UBC and SCCB have higher frequencies of high TMB and PD-L1 expression than ACB and SCCB has the highest frequency of CD274amplification. Neoadjuvant pembrolizumab showed preliminary activity in SCCB. Further study of IO biomarkers in coordination with therapy response and inclusion of SCCB appear warranted in perioperative IO trials. Legal entity responsible for the studyFoundation Medicine. FundingFoundation Medicine. DisclosureJ.S. Ross: Full / Part-time employment: Foundation Medicine. S.M. Ali: Full / Part-time employment: Foundation Medicine. J. Chung: Full / Part-time employment: Foundation Medicine. A.B. Schrock: Full / Part-time employment: Foundation Medicine. R. Madison: Full / Part-time employment: Foundation Medicine. B.M. Alexander: Full / Part-time employment: Foundation Medicine. A. Necchi: Advisory / Consultancy: Merck; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy: Bayer. All other authors have declared no conflicts of interest.