Impact of PD‐L1 and T‐cell inflamed gene expression profile on survival in advanced ovarian cancer. Issue 7 (July 2020)

• Record Type: Journal Article
• Authors: Høgdall, Estrid; Høgdall, Claus; Vo, Thao; Zhou, Wei; Huang, Lingkang; Marton, Matthew; Keefe, Stephen M; Busch‐Sørensen, Michael; Sørensen, Sarah M.; Georgsen, Jeanette; Mejlgaard, Else; Nedergaard, Lotte; Steiniche, Torben
• Is Part Of: International journal of gynecological cancer. Volume 30:Issue 7(2020)
• Publication Date: 2020-07
• Subjects: medical oncology; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2019-001109
• Languages: English
• ISSNs: 1048-891X

Abstract

ABSTRACT : Objective : Programmed death ligand 1 (PD‐L1) expression affects tumor evasion of immune surveillance. The prognostic value and relationship of PD‐L1 expression to T‐cell‐inflamed immune signatures in ovarian cancer are unclear. The purpose of this study is to evaluate the impact of PD‐L1 on overall survival and its correlation with an immune‐mediated gene expression profile in patients with advanced ovarian cancer. Methods : PD‐L1 expression in tumor and immune cells was assessed by immunohistochemistry, and PD‐L1‐positive expression was defined as a combined positive score ≥1; a T‐cell‐inflamed gene expression profile containing interferon γ response genes was evaluated using extracted RNA from surgical samples. Associations between PD‐L1 expression, gene expression profile status, and overall survival were analyzed using the Kaplan‐Meier method, log‐rank test, and multivariate Cox proportional hazards regression models. Results : A total of 376 patients with advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer treated by cytoreductive surgery and platinum‐based therapy were included. PD‐L1‐positive expression was observed in 50.5% of patients and associated with more advanced stage (p=0.047), more aggressive histologic subtype (p=0.001), and platinum sensitivity defined by increasing treatment‐free interval from first platinum‐based chemotherapy to next systemic treatment (p=0.027). PD‐L1‐positive expression was associated with longer overall survival in multivariate analyses (adjusted HR 0.72, 95% CI 0.56 to 0.93). In subgroup analyses, this association was most pronounced in patients with partially platinum‐sensitive disease (treatment‐free interval ≥6 to <12 months). T‐cell‐inflamed gene expression profile status correlated with PD‐L1 expression (Spearman, ρ =0.712) but was not an independent predictor of overall survival. Conclusion : PD‐L1 expression is associated with longer overall survival among advanced ovarian cancer patients. PD‐L1 expression may be an independent prognostic biomarker.