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Emulation of the KEYNOTE-189 Trial Using Electronic Health Records

Completed
Conditions
Non-small Cell Lung Cancer
Metastatic Lung Cancer
Interventions
Registration Number
NCT05908799
Lead Sponsor
Aetion, Inc.
Brief Summary

Investigators are building an empirical evidence base supporting the utility of real-world data through the emulation of randomized controlled trials in the oncology setting. The purpose of this work is to demonstrate whether real-world evidence studies can provide reliable conclusions on treatment effectiveness to inform further applications of real-world data in pharmaceutical product label expansion, post-marketing safety, and other purposes that are complementary to RCTs.

Detailed Description

This is a non-randomized observational study that is being conducted as a part of the Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation (CARE) Initiative, a multi-stakeholder collaboration led by Aetion. The study is intended to emulate the trial listed below/above. Although many features of the trial cannot be directly replicated in real-world data sources, key elements of the study design, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial as closely as possible. Investigators assume that the trial provides the reference standard treatment effect estimate and that failure to replicate trial findings is indicative of the inadequacy of the real-world data source for replication for a range of possible reasons and does not provide information on the validity of the original trial finding.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1854
Inclusion Criteria
  • Has evidence in electronic health record indicating a 'lung' tumor site, non-squamous morphology (e.g., adenocarcinoma, large cell, etc), and a stage IV or metastatic disease in the form of diagnosis codes or derived variables from physician notes or linked data from a tumor registry. There is no evidence of other lung cancer types (i.e., mesothelioma, small cell, etc.).
  • Does not have evidence of HGVS codes in health record indicating EGFR or ALK mutations.
  • Has no evidence of use of guideline-recommended systemic cancer therapy* for NSCLC on or after first date associated with stage IV (or metastatic) disease and prior to index treatment.
Exclusion Criteria
  • Has evidence of squamous cell lung cancer morphology in the form of diagnosis codes or derived variables from physician notes or linked information from a tumor registry.
  • Has evidence of systemic cancer therapy utilization on or after first date associated with stage IV (or metastatic) disease and prior to index treatment. Patient has no evidence of biologic therapy at any time prior to the first record indicating an exposure of interest.
  • Has evidence in medical record or tumor registry of primary malignancies beyond the lung tissue, except basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
  • Has evidence of central nervous system (CNS) metastases and/or carcinomatous meningitis in the 2 weeks prior to initiation.
  • Has a record of use of one of the following agents in the 2 years prior to the index date: methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, azathioprine, etanercept, adalimumab, infliximab, certolizumab, golimumab, anakinra, tocilizumab, sarilumumab, abatacept, rituximab, tofacitinib, barivitinib, upadacitinib, mycophenolate.
  • Has at least two records 60 days apart indicating use of one of the following agents in the 3 months prior to the index date: prednisone, prednisolone, methylprednisolone, dexamethasone, hydrocortisone.
  • Has evidence of use of one of the following agents prior to the index date: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Pembrolizumab + ChemotherapyPembrolizumab + Pemetrexed-PlatinumExposure Group
ChemotherapyPemetrexed-PlatinumReference Group
Primary Outcome Measures
NameTimeMethod
Overall Survival - Mortality Hazard RatioThrough study completion (earliest of 640 days or censoring)

Relative hazard of mortality due to any cause

Overall Survival - Mortality Risk1 year, year 1

12-month survival probability

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Aetion

🇺🇸

Boston, Massachusetts, United States

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