| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | European Urology | ||||
| Publisher: | ELSEVIER | ||||
| Place of Publication: | AMSTERDAM | ||||
| Volume: | 83 | ||||
| Number of Issue or Book Chapter: | 2 | ||||
| Page Range: | pp. 133-142 | ||||
| Date: | 2023 | ||||
| Institutions: | Medicine > Lehrstuhl für Urologie | ||||
| Identification Number: |
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| Keywords: | OPEN-LABEL; CHEMOTHERAPY; PEMBROLIZUMAB; ATEZOLIZUMAB; MULTICENTER; THERAPY; PLACEBO; Urothelial cancer; Metastatic urothelial cancer; Immune therapy; Immune microenvironment; Subtypes | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 76184 |
Web of ScienceAbstract
Background: The value of programmed cell death ligand-1 (PD-L1) to predict durable responses to immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) is inconsistent. We hypothesize that the use of archived primary tumor material (PRIM) for PD-L1 testing in clinical trials not properly reflecting the metastatic disease status (MET) contributes to this clinical issue. ...
Abstract
Background: The value of programmed cell death ligand-1 (PD-L1) to predict durable responses to immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) is inconsistent. We hypothesize that the use of archived primary tumor material (PRIM) for PD-L1 testing in clinical trials not properly reflecting the metastatic disease status (MET) contributes to this clinical issue. Objective: To analyze the predictive and prognostic value of PD-L1, spatial immunepheno-types, and major histocompatibility complex class I (MHC-I) determined in patient -matched PRIM/MET.Design, setting, and participants: PD-L1, spatial immunephenotypes, and MHC-I were examined in 154 mUC patients with at least one available pretreatment MET (138 patient-matched PRIM/MET pairs). Outcome measurements and statistical analysis: PD-L1, spatial immunephenotype, and MHC-I status of (patient-matched PRIM and) pretreatment MET were correlated with chemotherapy and ICI response and outcomes.Results and limitations: Discordance rates in patient-matched PRIM/MET were 25/30%, 36%, and 49% for PD-L1 (CPS10/IC5%), immunephenotypes, and MHC-I (loss vs pre-served), respectively. Correlations with chemotherapy and ICI responses were observed for immunephenotypes and MHC-I status determined in MET (not for PD-L1 alone), but not in PRIM. In case of ICIs, patients with cytotoxic tumor immune microenvironment (TIME) showed durable responses with disease control rates of 90% and a hazard ratio for disease progression/death of 0.05 (95% confidence interval: 0.01-0.65) versus patients with immunedepleted MET (disease control rate 29%). MET MHC-I status added an incremental value to predict durable ICI responses. Limitations include the partly ret-rospective design and the lack of MET multisampling on individual patient level.Conclusions: The TIME is subject to substantial dynamics during metastatic evolution. MET immunephenotypes and MHC-I statuses show promising potential to predict chemotherapy and durable ICI responses, while the PRIM TIME does not. Thus, future clinical trials should rather rely on pretreatment MET biopsies reflecting the current immunological disease state than on PRIM.Patient summary: Prediction of chemotherapy and responses to immune checkpoint inhibitors might be possible using representative pretreatment metastatic biopsies.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).
Metadata last modified: 18 Mar 2025 10:10
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