Abstract 485P
Background
Patients with expressing PD-L1 benefit from immune checkpoint inhibitors (ICIs); however, several challenges remain associated with PD-L1 testing. Herein, we investigates the concordance between PD-L1 expression by immunohistochemistry (IHC) and next-generation sequencing (RNA-seq) as well as its correlation with outcomes.
Methods
1,416 esophageal adenocarcinomas (EA), 486 esophageal squamous carcinomas (ES), 859 esophagogastric junction adenocarcinomas (EJA), and 1,613 gastric adenocarcinoma (GA) samples were analyzed using NGS of DNA (NextSeq, 592 genes and NovaSeq, WES) and RNA (NovaSeq, WTS). PD-L1 IHC positivity was defined as ≥1% CPS (Agilent's 22c3). Correlation between PD-L1 CPS and CD274 expression were assessed by Spearman’s coefficient. Tumors were divided into CD274-H (high expression - the top 25%) and CD274-L (low expression - bottom 25%) cohorts. Real-world overall survival (OS) data were obtained from insurance claims records.
Results
PD-L1 CPS and CD274 expression are weakly correlated in adenoca (EA: 0.374, EJA: 0.358, GA: 0.387), while a stronger correlation was found in squamous (ES: 0.537). Median CD274 expression was significantly higher in PD-L1+ compared to PD-L1- ES tumors and in EA, EJA, and GA tumors (p < .001). In PD-L1 IHC-negative ES, there was no association between CD274-H expression and OS (H 12.4 vs L 10.6 mo; HR 0.90, p .48). However, in adenoca, CD274-H showed a slightly improved OS (12.8 vs 11.3 mo; HR 0.79, p < 0.05). CD274-H was associated with improved post-CP/nivolumab survival in ES (96.5 vs 28 mo; HR 0.32; p .047), with a similar pattern in Adeno EGC (NR vs 30.2 mo; HR 0.39, p = 0.23). Furthermore, in CD274-L GEC, there was no difference in post-treatment survival with the addition of Nivolumab to CP (Squamous: 30 vs 18.2 mo; HR 0.91, p .83; Adeno: 30.2 vs 27.4 mo; HR 1.14; p .76). CD274-H showed improved survival with the addition of Nivolumab (Squamous: 96.5 vs 13.8 mo; HR 0.15; p .01; Adeno: NR vs 18.2 mo; HR 0.30; p .08).
Conclusions
High CD274 expression was associated with improved survival when Nivolumab was added to chemotherapy in patients with PD-L1-negative tumors. Further investigation is needed to confirm the potential benefit of Nivolumab in PD-L1-negative but high mRNA expression.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Wu, J. Xiu, S.K. Deshmukh: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences. All other authors have declared no conflicts of interest.