2232O Atezolizumab (atezo) and tumour microenvironment in early triple-negative breast cancer (eTNBC): Exploratory biomarker analysis from IMpassion031

IMpassion031 showed that neoadjuvant chemotherapy (CT) + atezo significantly increased pathological complete response (pCR) and numerically favoured event-free, disease-free and overall survival (EFS, DFS and OS) vs CT + placebo (Pla) in patients (pts) with eTNBC. This IMpassion031 substudy assessed potential predictive tumour immune biomarkers for atezo clinical benefit. Biomarker evaluation was performed on baseline, on-treatment, surgery and disease recurrence matched formalin-fixed, paraffin-embedded tumour tissue samples. Samples were tested for tumour infiltrating lymphocytes (TILs) and with RNA sequencing to derive molecular subtypes (basal-like immune activated [BLIA], basal-like immune suppressed [BLIS], mesenchymal [MES], luminal androgen receptor [LAR]), biological pathways and cellular components (xCELL). Biomarkers were evaluated for their association with pCR, EFS, DFS and OS. In patients with TIL-low tumours, atezo numerically improved outcomes compared with Pla (ΔpCR =19.4%, EFS hazard ratio [HR] 0.57, DFS HR 0.64 and OS HR 0.31). Atezo had higher pCR than Pla in BLIA (75% vs 54%) and BLIS (54% vs 32%) subtypes but not in LAR (33% vs 33%). While atezo showed improved EFS (HR 0.38) and DFS (HR 0.24) only in pts with BLIA tumours, atezo OS improvement vs Pla was only seen in pts with BLIS tumours (HR 0.17). The LAR subtype had excellent EFS, DFS and OS regardless of treatment, in contrast to a relatively low pCR rate. Biological pathway and cell type analyses indicated that increased proliferation, γδ T cells and pro-B cells predict atezo pCR benefit, while epithelial-mesenchymal transition, pericytes and stromal biology (e.g. angiogenesis, TGFβ) are linked to lack of atezo pCR benefit. No biological pathway or cell type consistently predicted atezo EFS, DFS or OS benefit. Exposure to CT ± atezo promoted dynamic changes in molecular subtype, which return to baseline at disease recurrence. Atezo provides benefit in eTNBC pts with proliferative basal tumours, but is less active in indolent LAR tumours. Atezo improves outcomes in pts with low TILs, a subgroup with poor prognosis in eTNBC. Further studies are needed to validate these findings.