CARE Initiative: Real-world Emulation of the KEYNOTE-189 Trial [DS3]

NCT06607393 | Completed FDA Drug

• 1 other identifier: DS3-KN189
• Study Type: observational
• Target: 851
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this non-interventional study is to emulate the KEYNOTE-189 randomized controlled trial of pembrolizumab for the treatment of metastatic non-small cell lung cancer using real-world, electronic health record data. The main questions this study aims to answer are:

1. 1.Do patients with metastatic non-small cell lung cancer (NSCLC) treated with pemetrexed, cisplatin/carboplatin, and pembrolizumab have improved real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) compared with patients treated with pemetrexed and cisplatin/carboplatin alone?
2. 2.How do the results of this non-interventional study compare to those of the KEYNOTE-189 randomized controlled trial?

Conditions

Metastatic Nonsmall Cell Lung Cancer

Keywords

real-world evidence; real-world data; oncology; pharmacoepidemiology; comparative effectiveness research; trial emulation

Outcome Measures

Primary Outcomes (2)

• Real-world overall survival (rwOS)

  Time from study treatment initiation to death

  From study treatment initiation until the date of death from any cause or censoring, whichever came first, assessed up to 20.4 months.

• Real-world progression-free survival (rwPFS)

  Time from study treatment initiation to disease progression or death

  From study treatment initiation until the date of disease progression, death from any cause or censoring, whichever came first, assessed up to 20.4 months.

Study Arms (2)

Exposed

Patients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC

Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Comparator

Patients initiating pemetrexed and cisplatin or carboplatin as first-line treatment for metastatic NSCLC

Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Interventions

Pembrolizumab DRUG

Exposed

Pemetrexed DRUG

Comparator; Exposed

Cisplatin DRUG

Comparator; Exposed

Carboplatin DRUG

Comparator; Exposed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients identified in the electronic health record data source with metastatic EGFR/ALK-negative non-small cell lung cancer initiating treatment with the study drugs (pemetrexed, cisplatin/carboplatin, pembrolizumab)

You may qualify if:

• Non-small cell lung cancer (NSCLC) diagnosis
• Histology not indicative of squamous cell carcinoma
• Metastatic disease
• Epidermal growth factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK)-negative or Kirsten rat sarcoma viral oncogene homolog (KRAS)-positive
• No prior systemic treatment for metastatic NSCLC
• No record of adjuvant or neoadjuvant therapy in the 12 months before metastatic diagnosis
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or missing or Karnofsky performance status \>=70 or missing
• No lab results indicating inadequate organ function, as defined in the KEYNOTE-189 RCT protocol

You may not qualify if:

• Histology indicative of squamous cell carcinoma or small cell elements
• Prior systemic treatment for metastatic NSCLC
• Prior antineoplastic biological therapy
• History of major cancer-related surgery in the 3 weeks before study drug initiation
• Radiation therapy to the lung \>30 Gy in the 6 months before study drug initiation
• Prior diagnosis of clinically active diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction
• Diagnosis of a second primary malignant neoplasm
• Diagnosis of brain, central nervous system, and/or spinal cord metastases
• Diagnosis of autoimmune disease and treatment with corticosteroids or immunosuppressive drugs after diagnosis and within the 2 years prior to study drug initiation
• Treatment with a non-topical systemic steroid in each of the 6 months prior to study drug initiation
• Prior treatment with pembrolizumab or any other anti-PD-1, PD-L1, PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms
• Treatment with non-topical antibiotics, antifungals, or antivirals within 2 weeks after an infection diagnosis in the month prior to study drug initiation
• Diagnosis of human immunodeficiency virus infection
• Diagnosis of acute hepatitis B or C
• Diagnosis of ascites or plural effusion in the 3 months prior to study drug initiation

Sponsors & Collaborators

• Aetion, Inc.: lead
• AbbVie: collaborator
• Amgen: collaborator
• AstraZeneca: collaborator
• Bayer: collaborator
• Gilead Sciences: collaborator
• Janssen, LP: collaborator
• Pfizer: collaborator

Related Publications (1)

• Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.

  PMID: 29658856 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

pembrolizumab; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2024
• First Posted: September 23, 2024
• Study Start: February 1, 2010
• Primary Completion: June 28, 2023
• Study Completion: June 28, 2023
• Last Updated: September 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share