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

Gonzalez‐Ericsson, P. I. et al. (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), pp. 667-684. (doi: 10.1002/path.5406) (PMID:32129476)

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.

• Item Type: Articles
• Additional Information: RS is supported by the Breast Cancer Research Foundation, New York, USA. SL is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. EAT is supported by the Breast Cancer Research Foundation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Le Quesne, Professor John
• Authors: 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., Hida, A. I., Balko, J. M., Haynes, H. R., Frahm, I., Acosta‐Haab, G., Balancin, M., Bellolio, E., Yang, W., Kirtani, P., Sugie, T., Ehinger, A., Castaneda, C. A., Kok, M., McArthur, H., Siziopikou, K., Badve, S., Fineberg, S., Gown, A., Viale, G., Schnitt, S. J., Pruneri, G., Penault‐Llorca, F., Hewitt, S., Thompson, E. A., Allison, K. H., Symmans, W. F., Bellizzi, A. M., Brogi, E., Moore, D. A., Larsimont, D., Dillon, D. A., Lazar, A., Lien, H., Goetz, M. P., Broeckx, G., El Bairi, K., Harbeck, N., Cimino‐Mathews, A., Sotiriou, C., Adams, S., Liu, S.‐w., Loibl, S., Chen, I.‐C., Lakhani, S. R., Juco, J. W., Denkert, C., Blackley, E. F., Demaria, S., Leon‐Ferre, R., Gluz, O., Zardavas, D., Emancipator, K., Ely, S., Loi, S., Salgado, R., and Sanders, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Pathology
• Publisher: Wiley
• ISSN: 0022-3417
• ISSN (Online): 1096-9896
• Published Online: 04 March 2020