Advancing the PD-L1 CPS test in metastatic TNBC: Insights from pathologists and findings from a nationwide survey

Crit Rev Oncol Hematol. 2023 Oct:190:104103. doi: 10.1016/j.critrevonc.2023.104103. Epub 2023 Aug 16.

Abstract

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC.

Keywords: 22C3; Biomarkers; Breast cancer; CPS; Immunotherapy; PD-L1; SP263; TNBC.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen*
  • Breast
  • Consensus
  • Humans
  • Pathologists
  • Triple Negative Breast Neoplasms* / diagnosis
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / genetics

Substances

  • B7-H1 Antigen