Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Hudeček 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., Laenkholm AV., Sharma A., Cimino-Mathews A., Srinivasan A., Acs B., Singh B., Calhoun B., Haibe-Kans B., Solomon B., Thapa B., Nelson BH., Gallas BD., Castaneda C., Ballesteros-Merino C., Criscitiello C., Boeckx C., Colpaert C., Quinn C., Chennubhotla CS., Swanton C., Solinas C., Hiley C., Drubay D., Bethmann D., Moore DA., Larsimont D., Sabanathan D., Peeters D., Zardavas D., Höflmayer D., Johnson DB., Thompson EA., Brogi E., Perez E., ElGabry EA., Stovgaard ES., Blackley EF., Roblin E., Reisenbichler E., Bellolio E., Balslev E., Chmielik E., Gaire F., Andre F., Lu FI., Azmoudeh-Ardalan F., Rojo F., Gruosso T., Ciompi F., Peale F.
© 2020, The Author(s). 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.