The evolving role of PD-L1 testing in patients with metastatic urothelial carcinoma

• Published in: Cancer treatment reviews Vol. 82; p. 101925
• Main Authors: Powles, Thomas, Walker, Jill, Andrew Williams, J., Bellmunt, Joaquim
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2020
• Subjects: Antibodies, Monoclonal, Humanized - classification; Antibodies, Monoclonal, Humanized - pharmacology; Antineoplastic Agents, Immunological - pharmacology; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; Biomarker; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - genetics; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - pathology; Gene Expression Profiling - methods; Humans; Immune checkpoint inhibitor; Neoplasm Metastasis; Neoplasm Staging; Patient Selection; Predictive Value of Tests; Prognosis; Prognostic; Programmed cell death ligand 1; Urologic Neoplasms - drug therapy; Urologic Neoplasms - pathology; Urothelial carcinoma; Programmed cell death ligand 1; Biomarker; Immune checkpoint inhibitor; Urothelial carcinoma; Prognostic
• ISSN: 0305-7372; 1532-1967; 1532-1967
• DOI: 10.1016/j.ctrv.2019.101925

•PD-L1 has emerged as an important cancer biomarker and target for immunotherapy in UC.•PD-L1 is frequently expressed on tumor cells and tumor-infiltrating immune cells.•Diagnostic assays are available, each with different scoring cutoffs to detect PD-L1.•Despite lack of assay standardization, PD-L1 expression can be reproducibly scored.•PD-L1 testing will increasingly guide treatment and should be discussed and offered to patients with UC. Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway improve clinical outcomes in patients with locally advanced/metastatic urothelial carcinoma (UC). PD-L1 complementary or companion diagnostic assays are now available for anti–PD-1 and anti–PD-L1 antibodies and these assays enable testing at diagnosis. The role of PD-L1 testing in UC is, however, the subject of much discussion within the medical community, particularly in light of recent restrictions on recruitment of PD-L1–low patients in clinical trials of atezolizumab and pembrolizumab as first-line therapy, and the European Medicines Agency and US Food and Drug Administration limiting use of these agents as first-line therapy in cisplatin-ineligible patients to those with high PD-L1 expression. We explore the evolving evidence for PD-L1 expression testing in UC and the role of PD-L1 expression in both tumor cells and tumor-infiltrating immune cells. We review clinical data on the prognostic and predictive value of PD-L1 expression in response to anti–PD-1/PD-L1 agents as first- and second-line therapy, considering issues such as the differences among complementary diagnostic assays in terms of the type of cells scored, antibodies used, and cutoff values. We consider how PD-L1 testing fits into decision-making and the potential of emerging biomarkers in UC. We conclude that, based on the scientific rationale for its use and evidence from clinical trials, PD-L1 testing provides enriched information on the patients most likely to benefit from immune checkpoint blockade and should be routinely offered to patients with metastatic UC.