Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1783497715435438080 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7020300 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT netterbergida tumortimecoursepredictsoverallsurvivalinnonsmallcelllungcancerpatientstreatedwithatezolizumabdependencyonfollowuptime AT brunorene tumortimecoursepredictsoverallsurvivalinnonsmallcelllungcancerpatientstreatedwithatezolizumabdependencyonfollowuptime AT chenyachi tumortimecoursepredictsoverallsurvivalinnonsmallcelllungcancerpatientstreatedwithatezolizumabdependencyonfollowuptime AT winterhelen tumortimecoursepredictsoverallsurvivalinnonsmallcelllungcancerpatientstreatedwithatezolizumabdependencyonfollowuptime AT lichichung tumortimecoursepredictsoverallsurvivalinnonsmallcelllungcancerpatientstreatedwithatezolizumabdependencyonfollowuptime AT jinjiny tumortimecoursepredictsoverallsurvivalinnonsmallcelllungcancerpatientstreatedwithatezolizumabdependencyonfollowuptime AT friberglenae tumortimecoursepredictsoverallsurvivalinnonsmallcelllungcancerpatientstreatedwithatezolizumabdependencyonfollowuptime |