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
Journal of Pathology
Journal Volume
250
Journal Issue
5
Pages
667-684
Date Issued
2020
Author(s)
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.
Goetz M.P.
Broeckx G.
El Bairi K.
Harbeck N.
Cimino-Mathews A.
Sotiriou C.
Adams S.
Liu S.-W.
Loibl S.
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.
Sanders M.
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. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
SDGs
Other Subjects
antineoplastic monoclonal antibody; atezolizumab; biological marker; capecitabine; durvalumab; nivolumab; paclitaxel; pembrolizumab; programmed death 1 ligand 1; programmed death 1 receptor; trastuzumab; vinorelbine tartrate; CD274 protein, human; programmed death 1 ligand 1; tumor marker; breast cancer; cancer immunology; cancer immunotherapy; cancer patient; clinical practice; clinical trial (topic); diagnostic test; human; immunocompetent cell; immunohistochemistry; overall survival; patient selection; phase 2 clinical trial (topic); phase 3 clinical trial (topic); preclinical study; priority journal; randomized controlled trial (topic); Review; risk assessment; risk management; treatment response; triple negative breast cancer; tumor associated leukocyte; immunology; metabolism; pathology; risk management; triple negative breast cancer; tumor associated leukocyte; B7-H1 Antigen; Biomarkers, Tumor; Humans; Lymphocytes, Tumor-Infiltrating; Risk Management; Triple Negative Breast Neoplasms
Publisher
John Wiley and Sons Ltd
Type
review