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

• Published in: Critical reviews in oncology/hematology 2023-10, Vol.190, p.104103, Article 104103
• Main Authors: Fusco, Nicola, Ivanova, Mariia, Frascarelli, Chiara, Criscitiello, Carmen, Cerbelli, Bruna, Pignataro, Maria Gemma, Pernazza, Angelina, Sajjadi, Elham, Venetis, Konstantinos, Cursano, Giulia, Pagni, Fabio, Di Bella, Camillo, Accardo, Marina, Amato, Michelina, Amico, Paolo, Bartoli, Caterina, Bogina, Giuseppe, Bortesi, Laura, Boldorini, Renzo, Bruno, Sara, Cabibi, Daniela, Caruana, Pietro, Dainese, Emanuele, De Camilli, Elisa, Dell’Anna, Vladimiro, Duda, Loren, Emmanuele, Carmela, Fanelli, Giuseppe Nicolò, Fernandes, Bethania, Ferrara, Gerardo, Gnetti, Letizia, Gurrera, Alessandra, Leone, Giorgia, Lucci, Raffaella, Mancini, Cristina, Marangi, Grazia, Mastropasqua, Mauro G., Nibid, Lorenzo, Orrù, Sandra, Pastena, Maria, Peresi, Monica, Perracchio, Letizia, Santoro, Angela, Vezzosi, Vania, Zambelli, Claudia, Zuccalà, Valeria, Rizzo, Antonio, Costarelli, Leopoldo, Pietribiasi, Francesca, Santinelli, Alfredo, Scatena, Cristian, Curigliano, Giuseppe, Guerini-Rocco, Elena, Martini, Maurizio, Graziano, Paolo, Castellano, Isabella, d'Amati, Giulia
• Format: Article
• Language: English
• Subjects: 22C3; Biomarkers; Breast cancer; CPS; Immunotherapy; PD-L1; SP263; TNBC
• ISSN: 1040-8428; 1879-0461; 1879-0461
• DOI: 10.1016/j.critrevonc.2023.104103

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. [Display omitted] •Breast pathologists face challenges in determining PD-L1 CPS score.•Lack of standardization across assays/staining platforms for PD-L1 CPS.•Validation and harmonization of the PD-L1 assays is crucial for consistent results.•Digital pathology may be of help, providing guidelines.•Infrastructures are present but challenges persist: harmonization, training.