Investigation of predictive biomarkers in patients treated with atezolizumab monotherapy following definitive chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma (EPOC1802)

416 Background: Platinum-based definitive chemoradiotherapy (dCRT) is the standard treatment for patients (pts) with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), invading the aorta, vertebral body, or trachea. However, complete response (CR) rates are low (11–25%), with a median overall survival (OS) of 9–10 months. We previously reported atezolizumab following dCRT indicated promising 42.1% of confirmed CR (cCR) rate and 65.8% of 12-months OS (Bando H, et al., ESMO Congress 2022 ). Methods: We investigated predictive biomarkers for cCR in this multicenter phase II study. PD-L1 tumor proportion score (TPS) was examined with VENTANA PD-L1. Immunological phenotypes of tumor microenvironments were assessed with multiplex immunohistochemistry (mIHC) and multi-color flow cytometry (FCM). Cancer gene aberrations and gene expression were investigated with whole exome and whole transcriptome sequencing (WES/WTS), respectively. Results: In 35 pts with an evaluable PD-L1 TPS, the cCR rates of +CD8+PD-1+ T cells and CD3+CD8-FOXP3+ T cells prior to CRT in tumor tissue were significantly correlated with cCR and non-cCR, respectively (both are P+CD8+ T cells prior to CRT, after CRT, and after atezolizumab were significantly correlated with cCR (P+FOXP3highCD45RA-CD4+ regulatory T cells (Treg cells) after CRT were significantly correlated with non-cCR (P+CD8+ T cells prior to CRT may be a predictive biomarker for cCR of CRT followed by atezolizumab, and that several driver gene abnormalities, cancer intrinsic signatures and tumor-infiltrating Treg cells are associated with treatment resistance. These findings could enable subsequent biomarker-selected clinical trials and lead to the development of novel cancer immunotherapeutic strategies. Clinical trial information: UMIN000034373 .