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Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data

PURPOSE: The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was to replicate control arms from four non–small cell lung cancer (NSCLC) randomized controlled...

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Autores principales: Ton, Thanh G.N., Pal, Navdeep, Trinh, Huong, Mahrus, Sami, Bretscher, Michael T., Machado, Robson J.M., Sadetsky, Natalia, Chaudhary, Nayan, Lu, Michael W., Riely, Gregory J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355621/
https://www.ncbi.nlm.nih.gov/pubmed/35511917
http://dx.doi.org/10.1158/1078-0432.CCR-22-0471
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author Ton, Thanh G.N.
Pal, Navdeep
Trinh, Huong
Mahrus, Sami
Bretscher, Michael T.
Machado, Robson J.M.
Sadetsky, Natalia
Chaudhary, Nayan
Lu, Michael W.
Riely, Gregory J.
author_facet Ton, Thanh G.N.
Pal, Navdeep
Trinh, Huong
Mahrus, Sami
Bretscher, Michael T.
Machado, Robson J.M.
Sadetsky, Natalia
Chaudhary, Nayan
Lu, Michael W.
Riely, Gregory J.
author_sort Ton, Thanh G.N.
collection PubMed
description PURPOSE: The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was to replicate control arms from four non–small cell lung cancer (NSCLC) randomized controlled trials (RCT) to analyze overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) using RWD. PATIENTS AND METHODS: This study used RWD from a nationwide de-identified database and a clinico-genomic database to replicate OS, PFS, and ORR endpoints in the chemotherapy control arms of four first-line NSCLC RCTs evaluating atezolizumab [IMpower150–wild-type (WT), IMpower130-WT, IMpower131, and IMpower132]. Additional objectives were to develop a definition of real-world PFS (rwPFS) and to evaluate the real-world response rate (rwRR) endpoint. RESULTS: Baseline demographic and clinical characteristics were balanced after application of propensity score weighting methods. For rwPFS and OS, RWD external controls were generally similar to their RCT control counterparts. Across all four trials, the hazard ratio (HR) point estimates comparing trial controls with external controls were closer to 1.0 for the PFS endpoint than for the OS endpoint. An exploratory assessment of rwRR in RWD revealed a slight but nonsignificant overestimation of RCT ORR, which was unconfounded by baseline characteristics. CONCLUSIONS: RWD can be used to reasonably replicate the OS and PFS of chemotherapy control arms of first-line NSCLC RCTs. Additional studies can provide greater insight into the utility of RWD in drug development.
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spelling pubmed-93556212023-01-05 Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data Ton, Thanh G.N. Pal, Navdeep Trinh, Huong Mahrus, Sami Bretscher, Michael T. Machado, Robson J.M. Sadetsky, Natalia Chaudhary, Nayan Lu, Michael W. Riely, Gregory J. Clin Cancer Res Clinical Trials: Immunotherapy PURPOSE: The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was to replicate control arms from four non–small cell lung cancer (NSCLC) randomized controlled trials (RCT) to analyze overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) using RWD. PATIENTS AND METHODS: This study used RWD from a nationwide de-identified database and a clinico-genomic database to replicate OS, PFS, and ORR endpoints in the chemotherapy control arms of four first-line NSCLC RCTs evaluating atezolizumab [IMpower150–wild-type (WT), IMpower130-WT, IMpower131, and IMpower132]. Additional objectives were to develop a definition of real-world PFS (rwPFS) and to evaluate the real-world response rate (rwRR) endpoint. RESULTS: Baseline demographic and clinical characteristics were balanced after application of propensity score weighting methods. For rwPFS and OS, RWD external controls were generally similar to their RCT control counterparts. Across all four trials, the hazard ratio (HR) point estimates comparing trial controls with external controls were closer to 1.0 for the PFS endpoint than for the OS endpoint. An exploratory assessment of rwRR in RWD revealed a slight but nonsignificant overestimation of RCT ORR, which was unconfounded by baseline characteristics. CONCLUSIONS: RWD can be used to reasonably replicate the OS and PFS of chemotherapy control arms of first-line NSCLC RCTs. Additional studies can provide greater insight into the utility of RWD in drug development. American Association for Cancer Research 2022-07-01 2022-05-05 /pmc/articles/PMC9355621/ /pubmed/35511917 http://dx.doi.org/10.1158/1078-0432.CCR-22-0471 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Clinical Trials: Immunotherapy
Ton, Thanh G.N.
Pal, Navdeep
Trinh, Huong
Mahrus, Sami
Bretscher, Michael T.
Machado, Robson J.M.
Sadetsky, Natalia
Chaudhary, Nayan
Lu, Michael W.
Riely, Gregory J.
Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data
title Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data
title_full Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data
title_fullStr Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data
title_full_unstemmed Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data
title_short Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data
title_sort replication of overall survival, progression-free survival, and overall response in chemotherapy arms of non–small cell lung cancer trials using real-world data
topic Clinical Trials: Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355621/
https://www.ncbi.nlm.nih.gov/pubmed/35511917
http://dx.doi.org/10.1158/1078-0432.CCR-22-0471
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