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

Paula Gonzalez-Ericsson , Elisabeth Stovgaard , Luz Sua , Emily Reisenbichler , Zuzana Kos , Jodi Carter , Stefan Michiels (1, 2) , John Le Quesne (3) , Torsten Nielsen , Anne-Vibeke Laenkholm (4) , Stephen Fox , Julien Adam , John Ms Bartlett , David Rimm , Cecily Quinn , Dieter Peeters , Maria Vittoria Dieci (5) , Anne Vincent-Salomon (6) , Ian Cree , Akira Hida , Justin M Balko (7) , Harry Haynes , Isabel Frahm , Gabriela Acosta-Haab , Marcelo Balancin , Enrique Bellolio , Wentao Yang , Pawan Kirtani , Tomoharu Sugie , Anna Ehinger (8) , Carlos Castaneda (9) , Marleen Kok (10) , Heather Mcarthur , Kalliopi Siziopikou , Sunil Badve , Susan Fineberg , Allen Gown , Giuseppe Viale (11) , Stuart Schnitt , Giancarlo Pruneri (12) , Frédérique Penault-Llorca (13, 14) , Stephen Hewitt , E Aubrey Thompson , Kimberly Allison , William Symmans , Andrew Bellizzi , Edi Brogi , David Moore (15) , Denis Larsimont (16) , Deborah Dillon , Alexander J Lazar (17) , Huangchun Lien , Matthew Goetz , Glenn Broeckx , Khalid El Bairi (18) , Nadia Harbeck (19) , Ashley Cimino-Mathews , Christos Sotiriou (16) , Sylvia Adams , Shi-Wei Liu , Sibylle Loibl (20) , I-Chun Chen , Sunil R Lakhani (21) , Jonathan Juco , Carsten Denkert (22) , Elizabeth Blackley , Sandra Demaria , Roberto Leon-Ferre , Oleg Gluz (23) , Dimitrios Zardavas (24) , Kenneth Emancipator , Scott Ely , Sherene Loi (25) , Roberto Salgado (25) , Melinda Sanders , Paula Gonzalez‐ericsson , Anne‐vibeke Lænkholm , Anne Vincent‐salomon , Gabriela Acosta‐haab , Frederique Penault‐llorca , Ashley Cimino‐mathews , Shi‐wei Liu , I‐chun Chen , Roberto Leon‐ferre

1 SBE - Service de biostatistique et d'épidémiologie
2 U1018 (Équipe 2) - Oncostat
3 University of Leicester
4 Department of Pathology
5 Unipd - Università degli Studi di Padova = University of Padua
6 Pharmacogenomics Unit [Paris]
7 Vanderbilt University Medical Center [Nashville]
8 Department of Pathology
9 Ctr Biomol Struct & Org
10 Department of Pathology
11 Division of Pathology and Laboratory Medicine
12 ESMO - European Institute of Oncology [Milan]
13 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
14 IMoST - Imagerie Moléculaire et Stratégies Théranostiques
15 Innovation North - Faculty of Information and Technology
16 Institut Jules Bordet [Bruxelles]
17 The University of Texas M.D. Anderson Cancer Center [Houston]
18 Université Mohamed 1 Oujda MAROC
19 Frauenklinik
20 GBG - German Breast Group
21 USQ - University of Southern Queensland
22 Charité, Institute of Pathology, Translational Tumorpathology Unit
23 West German Study Group
24 BIG aisbl - Breast International Group [Brussels, Belgium]
25 Breast Cancer Translational Research Laboratory

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.

Mots clés: PD-L1; TILs; biomarker risk-management; breast cancer; immunotherapy

Domaines: Sciences du Vivant [q-bio]; Cancer

Paula Gonzalez-Ericsson, Elisabeth Stovgaard, Luz Sua, Emily Reisenbichler, Zuzana Kos, et al.. 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. Journal of Pathology, 2020, 250 (5), pp.667-684. ⟨10.1002/path.5406⟩. ⟨hal-02882150⟩