Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Jan Hudecek; Leonie Voorwerk; Maartje van Seijen; Iris Nederlof; Michiel de Maaker; Jose van den Berg; Koen K. van de Vijver; Karolina Sikorska; Sylvia Adams; Sandra Demaria; Giuseppe Viale; Torsten O. Nielsen; Sunil S. Badve; Stefan Michiels; William Fraser Symmans; Christos Sotiriou; David L. Rimm; Stephen M. Hewitt; Carsten Denkert; Sibylle Loibl; Sherene Loi; John M.S. Bartlett; Giancarlo Pruneri; Deborah A. Dillon; Maggie C.U. Cheang; Andrew Tutt; Jacqueline A. Hall; Zuzana Kos; Roberto Salgado; Marleen Kok; Hugo M. Horlings; Aini Hyytiäinen; Akira I. Hida; Alastair Thompson; Alex Lefevre; Alexander J. Lazar; Allen Gown; Amy Lo; Anna Sapino; Anant Madabhushi; Andre Moreira; Andrea Richardson; Andrea Vingiani; Andrew H. Beck; Andrew M. Bellizzi; Angel Guerrero; Anita Grigoriadis; Anna Ehinger; Ana Garrido-Castro; Anne Vincent-Salomon; International Immuno-Oncology Biomarker Working Group; Loes Kooreman

doi:10.1038/s41523-020-0155-1

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Jan Hudecek, Leonie Voorwerk, Maartje van Seijen, Iris Nederlof, Michiel de Maaker, Jose van den Berg, Koen K. van de Vijver, Karolina Sikorska, Sylvia Adams, Sandra Demaria, Giuseppe Viale, Torsten O. Nielsen, Sunil S. Badve, Stefan Michiels, William Fraser Symmans, Christos Sotiriou, David L. Rimm, Stephen M. Hewitt, Carsten Denkert, Sibylle LoiblSherene Loi, John M.S. Bartlett, Giancarlo Pruneri, Deborah A. Dillon, Maggie C.U. Cheang, Andrew Tutt, Jacqueline A. Hall, Zuzana Kos, Roberto Salgado^*, Marleen Kok, Hugo M. Horlings, Aini Hyytiäinen, Akira I. Hida, Alastair Thompson, Alex Lefevre, Alexander J. Lazar, Allen Gown, Amy Lo, Anna Sapino, Anant Madabhushi, Andre Moreira, Andrea Richardson, Andrea Vingiani, Andrew H. Beck, Andrew M. Bellizzi, Angel Guerrero, Anita Grigoriadis, Anna Ehinger, Ana Garrido-Castro, Anne Vincent-Salomon, International Immuno-Oncology Biomarker Working Group, Loes Kooreman

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.

Original language	English
Article number	15
Number of pages	8
Journal	npj Breast Cancer
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41523-020-0155-1
Publication status	Published - 12 May 2020

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Hudecek, J., Voorwerk, L., van Seijen, M., Nederlof, I., de Maaker, M., van den Berg, J., van de Vijver, K. K., Sikorska, K., Adams, S., Demaria, S., Viale, G., Nielsen, T. O., Badve, S. S., Michiels, S., Symmans, W. F., Sotiriou, C., Rimm, D. L., Hewitt, S. M., Denkert, C., ... Kooreman, L. (2020). Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials. npj Breast Cancer, 6(1), Article 15. https://doi.org/10.1038/s41523-020-0155-1

@article{be9610748f804755a5a4f7946d71767a,

title = "Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials",

abstract = "Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.",

author = "Jan Hudecek and Leonie Voorwerk and {van Seijen}, Maartje and Iris Nederlof and {de Maaker}, Michiel and {van den Berg}, Jose and {van de Vijver}, {Koen K.} and Karolina Sikorska and Sylvia Adams and Sandra Demaria and Giuseppe Viale and Nielsen, {Torsten O.} and Badve, {Sunil S.} and Stefan Michiels and Symmans, {William Fraser} and Christos Sotiriou and Rimm, {David L.} and Hewitt, {Stephen M.} and Carsten Denkert and Sibylle Loibl and Sherene Loi and Bartlett, {John M.S.} and Giancarlo Pruneri and Dillon, {Deborah A.} and Cheang, {Maggie C.U.} and Andrew Tutt and Hall, {Jacqueline A.} and Zuzana Kos and Roberto Salgado and Marleen Kok and Horlings, {Hugo M.} and Aini Hyyti{\"a}inen and Hida, {Akira I.} and Alastair Thompson and Alex Lefevre and Lazar, {Alexander J.} and Allen Gown and Amy Lo and Anna Sapino and Anant Madabhushi and Andre Moreira and Andrea Richardson and Andrea Vingiani and Beck, {Andrew H.} and Bellizzi, {Andrew M.} and Angel Guerrero and Anita Grigoriadis and Anna Ehinger and Ana Garrido-Castro and Anne Vincent-Salomon and {International Immuno-Oncology Biomarker Working Group} and Loes Kooreman",

note = "Funding Information: The Department of Pathology of the Netherlands Cancer Institute is thanked for the support of this study and ensuring the rapid turnaround times. The Breast Cancer Research Foundation and Bristol-Myers-Squibb (BMS) are thanked for financial support. We also thank the BMS-International Immuno-Oncology Network (BMS/II-ON) and the Dutch Cancer Society (NKI2015-7710) for funding the clinical trial costs and this feasibility study (NKI2016-10510). S.L., R.S., and M.K. are supported by a grant from the Breast Cancer Research Foundation (BCRF, NY, US). The following is a list of current members of the International Immuno-Oncology Working Group (TILs Working Group). A member is defined as a person willing to be involved, informed and be part of the activities of the TILs Working Group. The authors alone are responsible for the views expressed in the work of the TIL Working Group and they do not necessarily represent the decisions, policy, or views of their employer. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = may,

day = "12",

doi = "10.1038/s41523-020-0155-1",

language = "English",

volume = "6",

journal = "npj Breast Cancer",

issn = "2374-4677",

publisher = "Nature Publishing Group",

number = "1",

}

Hudecek, J, Voorwerk, L, van Seijen, M, Nederlof, I, de Maaker, M, van den Berg, J, van de Vijver, KK, Sikorska, K, Adams, S, Demaria, S, Viale, G, Nielsen, TO, Badve, SS, Michiels, S, Symmans, WF, Sotiriou, C, Rimm, DL, Hewitt, SM, Denkert, C, Loibl, S, Loi, S, Bartlett, JMS, Pruneri, G, Dillon, DA, Cheang, MCU, Tutt, A, Hall, JA, Kos, Z, Salgado, R, Kok, M, Horlings, HM, Hyytiäinen, A, Hida, AI, Thompson, A, Lefevre, A, Lazar, AJ, Gown, A, Lo, A, Sapino, A, Madabhushi, A, Moreira, A, Richardson, A, Vingiani, A, Beck, AH, Bellizzi, AM, Guerrero, A, Grigoriadis, A, Ehinger, A, Garrido-Castro, A, Vincent-Salomon, A, International Immuno-Oncology Biomarker Working Group & Kooreman, L 2020, 'Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials', npj Breast Cancer, vol. 6, no. 1, 15. https://doi.org/10.1038/s41523-020-0155-1

TY - JOUR

T1 - Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

AU - Hudecek, Jan

AU - Voorwerk, Leonie

AU - van Seijen, Maartje

AU - Nederlof, Iris

AU - de Maaker, Michiel

AU - van den Berg, Jose

AU - van de Vijver, Koen K.

AU - Sikorska, Karolina

AU - Adams, Sylvia

AU - Demaria, Sandra

AU - Viale, Giuseppe

AU - Nielsen, Torsten O.

AU - Badve, Sunil S.

AU - Michiels, Stefan

AU - Symmans, William Fraser

AU - Sotiriou, Christos

AU - Rimm, David L.

AU - Hewitt, Stephen M.

AU - Denkert, Carsten

AU - Loibl, Sibylle

AU - Loi, Sherene

AU - Bartlett, John M.S.

AU - Pruneri, Giancarlo

AU - Dillon, Deborah A.

AU - Cheang, Maggie C.U.

AU - Tutt, Andrew

AU - Hall, Jacqueline A.

AU - Kos, Zuzana

AU - Salgado, Roberto

AU - Kok, Marleen

AU - Horlings, Hugo M.

AU - Hyytiäinen, Aini

AU - Hida, Akira I.

AU - Thompson, Alastair

AU - Lefevre, Alex

AU - Lazar, Alexander J.

AU - Gown, Allen

AU - Lo, Amy

AU - Sapino, Anna

AU - Madabhushi, Anant

AU - Moreira, Andre

AU - Richardson, Andrea

AU - Vingiani, Andrea

AU - Beck, Andrew H.

AU - Bellizzi, Andrew M.

AU - Guerrero, Angel

AU - Grigoriadis, Anita

AU - Ehinger, Anna

AU - Garrido-Castro, Ana

AU - Vincent-Salomon, Anne

AU - International Immuno-Oncology Biomarker Working Group

AU - Kooreman, Loes

N1 - Funding Information: The Department of Pathology of the Netherlands Cancer Institute is thanked for the support of this study and ensuring the rapid turnaround times. The Breast Cancer Research Foundation and Bristol-Myers-Squibb (BMS) are thanked for financial support. We also thank the BMS-International Immuno-Oncology Network (BMS/II-ON) and the Dutch Cancer Society (NKI2015-7710) for funding the clinical trial costs and this feasibility study (NKI2016-10510). S.L., R.S., and M.K. are supported by a grant from the Breast Cancer Research Foundation (BCRF, NY, US). The following is a list of current members of the International Immuno-Oncology Working Group (TILs Working Group). A member is defined as a person willing to be involved, informed and be part of the activities of the TILs Working Group. The authors alone are responsible for the views expressed in the work of the TIL Working Group and they do not necessarily represent the decisions, policy, or views of their employer. Publisher Copyright: © 2020, The Author(s).

PY - 2020/5/12

Y1 - 2020/5/12

N2 - Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.

AB - Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.

U2 - 10.1038/s41523-020-0155-1

DO - 10.1038/s41523-020-0155-1

M3 - (Systematic) Review article

SN - 2374-4677

VL - 6

JO - npj Breast Cancer

JF - npj Breast Cancer

IS - 1

M1 - 15

ER -

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

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