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

International Immuno-Oncology Biomarker Working Group

doi:10.1038/s41523-020-0155-1

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

International Immuno-Oncology Biomarker Working Group

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

8 Scopus citations

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
Journal	npj Breast Cancer
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41523-020-0155-1
State	Published - 1 Dec 2020

Bibliographical 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:
© 2020, The Author(s).

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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 = "{International Immuno-Oncology Biomarker Working Group} and Jan Hude{\v c}ek 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 Carlos Castaneda",

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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 - Castaneda, Carlos

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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.

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DO - 10.1038/s41523-020-0155-1

M3 - Artículo de revisión

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SN - 2374-4677

VL - 6

JO - npj Breast Cancer

JF - npj Breast Cancer

IS - 1

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ER -

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

Abstract

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