Exploratory biological analyses
cancers, Tumour, T-cell inflammation, tumour
CANCERS, TUMOUR, MICROSATELLITE INSTABILITY, TUMOUR, INFILTRATING, APPENDIX
Where available, prior germline testing results were retrieved for all patients. When HRR alterations identified at screening met bioinformatic thresholds for potentially germline, germline testing was performed. Determination of a post hoc HRR defect score was planned but could not be undertaken due to tissue and sequencing assay limitations. Similarly, microsatellite instability status was also not evaluable.Tumour mutational burden (TMB) has variable predictive capacity for immunotherapy benefit across a range of tumour types [Tumour cell (PD-L1) expression was evaluated by immunohistochemistry using the Ventana PD-L1 (SP263) assay with cut-offs for positivity set at ≥1%. Archival tumour tissue was used to assess tumour infiltrating lymphocytes (TILs) and gene expression signatures corresponding to T-cell inflammation [The neutrophil:lymphocyte ratio (NLR) was determined using a baseline full blood count, defined as the ratio of absolute neutrophil count to absolute lymphocyte count, with a cut-off of four selected based on published thresholds for clinical benefit from immune checkpoint inhibition across various cancers [Peripheral blood mononuclear cells (PBMC) collected at baseline, week 4 and week 8 were stained for immune markers of interest using multiparametric flow cytometry and screened for putative variables associated with treatment benefit. Data were acquired using LSR II Fortessa and FACS Diva software. Immunophenotyping data were analysed using FlowJo 199 (BD v10.6.2). For detailed information on optimised panels, refer to Appendix 