The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice
Authors: Gonzalez‐Ericsson Paula I , Stovgaard Elisabeth S , Sua Luz F , Reisenbichler Emily , Kos Zuzana , Carter Jodi M , Michiels Stefan , Le Quesne John , Nielsen Torsten O , Lænkholm Anne‐Vibeke , Fox Stephen B , Adam Julien , Bartlett John MS , Rimm David L , Quinn Cecily , Peeters Dieter , Dieci Maria V , Vincent‐Salomon Anne , Cree Ian , Hida Akira I , Balko Justin M , Haynes Harry R , Frahm Isabel , Acosta‐Haab Gabriela , Balancin Marcelo , Bellolio Enrique , Yang Wentao , Kirtani Pawan , Sugie Tomoharu , Ehinger Anna , Castaneda Carlos A , Kok Marleen , McArthur Heather , Siziopikou Kalliopi , Badve Sunil , Fineberg Susan , Gown Allen , Viale Giuseppe , Schnitt Stuart J , Pruneri Giancarlo , Penault‐Llorca Frederique , Hewitt Stephen , Thompson E Aubrey , Allison Kimberly H , Symmans William F , Bellizzi Andrew M , Brogi Edi , Moore David A , Larsimont Denis , Dillon Deborah A , Lazar Alexander , Lien Huangchun , Goetz Matthew P , Broeckx Glenn , El Bairi Khalid , Harbeck Nadia , Cimino‐Mathews Ashley , Sotiriou Christos , Adams Sylvia , Liu Shi‐wei , Loibl Sibylle , Chen I‐Chun , Lakhani Sunil R , Juco Jonathan W , Denkert Carsten , Blackley Elizabeth F , Demaria Sandra , Leon‐Ferre Roberto , Gluz Oleg , Zardavas Dimitrios , Emancipator Kenneth , Ely Scott , Loi Sherene , Salgado Roberto , Sanders Melinda ,   International Immuno‐Oncology Biomarker Working Group
Published: March 2020

Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.