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Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time

The large heterogeneity in response to immune checkpoint inhibitors is driving the exploration of predictive biomarkers to identify patients who will respond to such treatment. We extended our previously suggested modeling framework of atezolizumab pharmacokinetics, IL18, and tumor size (TS) dynamic...

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Autores principales: Netterberg, Ida, Bruno, René, Chen, Ya‐Chi, Winter, Helen, Li, Chi‐Chung, Jin, Jin Y., Friberg, Lena E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020300/
https://www.ncbi.nlm.nih.gov/pubmed/31991070
http://dx.doi.org/10.1002/psp4.12489
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author Netterberg, Ida
Bruno, René
Chen, Ya‐Chi
Winter, Helen
Li, Chi‐Chung
Jin, Jin Y.
Friberg, Lena E.
author_facet Netterberg, Ida
Bruno, René
Chen, Ya‐Chi
Winter, Helen
Li, Chi‐Chung
Jin, Jin Y.
Friberg, Lena E.
author_sort Netterberg, Ida
collection PubMed
description The large heterogeneity in response to immune checkpoint inhibitors is driving the exploration of predictive biomarkers to identify patients who will respond to such treatment. We extended our previously suggested modeling framework of atezolizumab pharmacokinetics, IL18, and tumor size (TS) dynamics, to also include overall survival (OS). Baseline and model‐derived variables were explored as predictors of OS in 88 patients with non‐small cell lung cancer treated with atezolizumab. To investigate the impact of follow‐up length on the inclusion of predictors of OS, four different censoring strategies were applied. The time‐course of TS change was the most significant predictor in all scenarios, whereas IL18 was not significant. Identified predictors of OS were similar regardless of censoring strategy, although OS was underpredicted when patients were censored 5 months after last dose. The study demonstrated that the tumor‐time course‐OS relationship could be identified based on early phase I data.
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spelling pubmed-70203002020-02-19 Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time Netterberg, Ida Bruno, René Chen, Ya‐Chi Winter, Helen Li, Chi‐Chung Jin, Jin Y. Friberg, Lena E. CPT Pharmacometrics Syst Pharmacol Research The large heterogeneity in response to immune checkpoint inhibitors is driving the exploration of predictive biomarkers to identify patients who will respond to such treatment. We extended our previously suggested modeling framework of atezolizumab pharmacokinetics, IL18, and tumor size (TS) dynamics, to also include overall survival (OS). Baseline and model‐derived variables were explored as predictors of OS in 88 patients with non‐small cell lung cancer treated with atezolizumab. To investigate the impact of follow‐up length on the inclusion of predictors of OS, four different censoring strategies were applied. The time‐course of TS change was the most significant predictor in all scenarios, whereas IL18 was not significant. Identified predictors of OS were similar regardless of censoring strategy, although OS was underpredicted when patients were censored 5 months after last dose. The study demonstrated that the tumor‐time course‐OS relationship could be identified based on early phase I data. John Wiley and Sons Inc. 2020-01-28 2020-02 /pmc/articles/PMC7020300/ /pubmed/31991070 http://dx.doi.org/10.1002/psp4.12489 Text en © 2020 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research
Netterberg, Ida
Bruno, René
Chen, Ya‐Chi
Winter, Helen
Li, Chi‐Chung
Jin, Jin Y.
Friberg, Lena E.
Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time
title Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time
title_full Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time
title_fullStr Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time
title_full_unstemmed Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time
title_short Tumor Time‐Course Predicts Overall Survival in Non‐Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow‐Up Time
title_sort tumor time‐course predicts overall survival in non‐small cell lung cancer patients treated with atezolizumab: dependency on follow‐up time
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020300/
https://www.ncbi.nlm.nih.gov/pubmed/31991070
http://dx.doi.org/10.1002/psp4.12489
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