In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 416-416
Abstract:
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 〈 1% and ≥1% were 44.4% and 41.2%, respectively. In mIHC analysis of 28 pts, the number of CD3 + 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 〈 0.05). In FCM analysis of 19 pts, tumor-infiltrating PD-1 + CD8 + T cells prior to CRT, after CRT, and after atezolizumab were significantly correlated with cCR (P 〈 0.05). On the other hand, CTLA-4 + FOXP3 high CD45RA - CD4 + regulatory T cells (Treg cells) after CRT were significantly correlated with non-cCR (P 〈 0.05). In WES of 27 pts, MYC amplification, EGFR mutation, PIK3CA mutation, PTEN mutation, and KEAP1 mutation were detected in pts with non-cCR. In WTS of 27 pts, gene expression signatures of IFN-γ response and inflammatory response were enhanced after CRT. Gene expression signatures of epithelial mesenchymal transition (EMT) and TGF-β signalings prior to CRT were significantly enriched in pts with cCR. Conclusions: Our biomarker analysis suggests that tumor-infiltrating PD-1 + 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 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.4_suppl.416
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5
