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Original research
Impact of PD-L1 and T-cell inflamed gene expression profile on survival in advanced ovarian cancer
  1. Estrid Høgdall1,
  2. Claus Høgdall2,
  3. Thao Vo3,
  4. Wei Zhou3,
  5. Lingkang Huang3,
  6. Matthew Marton3,
  7. Stephen M Keefe3,
  8. Michael Busch-Sørensen4,
  9. Sarah M. Sørensen2,
  10. Jeanette Georgsen5,
  11. Else Mejlgaard5,
  12. Lotte Nedergaard6 and
  13. Torben Steiniche5
  1. 1Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
  2. 2Department of Gynecology and Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  3. 3Merck & Co., Inc, Kenilworth, New Jersey, USA
  4. 4Busch-Sørensen Consulting, Virum, Denmark
  5. 5Department of Pathology, Aarhus University Hospital, Aarhus, Denmark
  6. 6Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Dr Estrid Høgdall, Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev 2730, Denmark; estrid.hoegdall{at}regionh.dk

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.

  • medical oncology

https://doi.org/10.1136/ijgc-2019-001109

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    Footnotes

    • Deceased Dr Lotte Nedergaard

    • Correction notice Since the online publication of this article, the title was updated to include the abbreviation 'PD-L1'

    • Contributors Conception, design, or planning of the study: EH, CH, TV, WZ, MM, SMK, MB, JG, LN, TS; acquisition of the data: EH, CH, TV, MB, SMS, JG, EM, TS; analysis of the data: CH, TV; interpretation of the results: EH, CH, TV, WZ, LH, MB, EM; provision of study materials: EH, CH, JG, TS; drafting of the manuscript: CH, TV, WZ, JG, TS; administrative, logistical, or technical support: EH, TV, WZ, MM, MB, TS; reviewing/revising manuscript for important intellectual content: EH, CH, TV, WZ, LH, MM, SMK, MB, SMS, EM, LN. All authors reviewed and approved the final version of the manuscript.

    • Funding Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

    • Competing interests TV, WZ, LH, and MM are employees and stockholders of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. MM received research funding from Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. SMK is an employee of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. EM received research funding from MSD during the conduct of the study and outside the submitted work. TS has received research funding from MSD, Denmark during the conduct of the study and research funds from MSD, Denmark, outside the submitted work.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement The Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA data sharing policy, including restrictions, is available at http://engagezone.msd.com/ds_documentation.php. Requests for access to the clinical study data can be submitted through the EngageZone site or via email to dataaccess@merck.com.