Journal article

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 Show all

npj Breast Cancer | NATURE RESEARCH | Published : 2020


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 ..

View full abstract


Awarded by Dutch Cancer Society

Awarded by Cancer Research UK

Funding Acknowledgements

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/IION) 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.