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 I. Gonzalez-Ericsson*, Elisabeth S. Stovgaard, Luz F. Sua, Emily Reisenbichler, Zuzana Kos, Jodi M. Carter, Stefan Michiels, John Le Quesne, Torsten O. Nielsen, Anne Vibeke Lænkholm, Stephen B. Fox, Julien Adam, John M.S. Bartlett, David L. Rimm, Cecily Quinn, Dieter Peeters, Maria V. Dieci, Anne Vincent-Salomon, Ian Cree, Akira I. HidaJustin M. Balko, Harry R. Haynes, Isabel Frahm, Gabriela Acosta-Haab, Marcelo Balancin, Enrique Bellolio, Wentao Yang, Pawan Kirtani, Tomoharu Sugie, Anna Ehinger, Carlos A. Castaneda, Marleen Kok, Heather McArthur, Kalliopi Siziopikou, Sunil Badve, Susan Fineberg, Allen Gown, Giuseppe Viale, Stuart J. Schnitt, Giancarlo Pruneri, Frederique Penault-Llorca, Stephen Hewitt, E. Aubrey Thompson, Kimberly H. Allison, William F. Symmans, Andrew M. Bellizzi, Edi Brogi, David A. Moore, Denis Larsimont, Deborah A. Dillon, Alexander Lazar, Huangchun Lien, Matthew P. Goetz, Glenn Broeckx, Khalid El Bairi, Nadia Harbeck, Ashley Cimino-Mathews, Christos Sotiriou, Sylvia Adams, Shi wei Liu, Sibylle Loibl, I. Chun Chen, Sunil R. Lakhani, Jonathan W. Juco, Carsten Denkert, Elizabeth F. Blackley, Sandra Demaria, Roberto Leon-Ferre, Oleg Gluz, Dimitrios Zardavas, Kenneth Emancipator, Scott Ely, Sherene Loi, Roberto Salgado, Melinda Sanders

*Corresponding author for this work

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)667-684
Number of pages18
JournalJournal of Pathology
Volume250
Issue number5
DOIs
StatePublished - Apr 1 2020

Keywords

  • PD-L1
  • TILs
  • biomarker risk-management
  • breast cancer
  • immunotherapy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Gonzalez-Ericsson, P. I., Stovgaard, E. S., Sua, L. F., Reisenbichler, E., Kos, Z., Carter, J. M., Michiels, S., Le Quesne, J., Nielsen, T. O., Lænkholm, A. V., Fox, S. B., Adam, J., Bartlett, J. M. S., Rimm, D. L., Quinn, C., Peeters, D., Dieci, M. V., Vincent-Salomon, A., Cree, I., ... Sanders, M. (2020). 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, 250(5), 667-684. https://doi.org/10.1002/path.5406