Replication of overall survival, progression-free survival, and overall response in chemotherapy arms of non-small cell lung cancer trials using real-world data Journal Article


Authors: Ton, T. G. N.; Pal, N.; Trinh, H.; Mahrus, S.; Bretscher, M. T.; Machado, R. J. M.; Sadetsky, N.; Chaudhary, N.; Lu, M. W.; Riely, G. J.
Article 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
Abstract: 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-wildtype (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. © 2022 The Authors.
Keywords: cancer chemotherapy; cancer survival; controlled study; treatment outcome; aged; survival rate; major clinical study; bevacizumab; cancer combination chemotherapy; drug efficacy; paclitaxel; cancer staging; outcome assessment; antineoplastic agent; carboplatin; progression free survival; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; proportional hazards models; randomized controlled trials as topic; lung tumor; proportional hazards model; drug response; hazard ratio; non small cell lung cancer; progression-free survival; randomized controlled trial (topic); propensity score; humans; human; male; female; article; electronic health record; atezolizumab
Journal Title: Clinical Cancer Research
Volume: 28
Issue: 13
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2022-07-01
Language: English
DOI: 10.1158/1078-0432.Ccr-22-0471
PUBMED: 35511917
PROVIDER: scopus
PMCID: PMC9355621
DOI/URL:
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
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  1. Gregory J Riely
    603 Riely