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

Aetion

Status

Completed

Conditions

Metastatic Nonsmall Cell Lung Cancer

Treatments

Drug: Pemetrexed

Drug: Cisplatin

Drug: Carboplatin

Drug: Pembrolizumab

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT06607393

DS3-KN189

Details and patient eligibility

About

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:

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?
How do the results of this non-interventional study compare to those of the KEYNOTE-189 randomized controlled trial?

Full description

The Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation (CARE) Initiative is a program designed to build an empirical evidence base for the use of real-world data (RWD) in clinical and regulatory decision-making. Using randomized controlled trials (RCTs) as a benchmark for causal effect estimates, a series of RCT emulations will be conducted across varying trials, real world data sources, and study design elements to better understand under what conditions non-interventional studies, using data generated during routine clinical care, can provide reliable conclusions about drug effectiveness.

In this study, real-world electronic health record (EHR) data will be used to emulate the KEYNOTE-189 efficacy trial of pembrolizumab as first-line therapy in patients with metastatic non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) sensitizing mutations. Similarly to the KEYNOTE-189 trial, this study will compare real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) between patients who initiate pemetrexed, platinum-based chemotherapy, and pembrolizumab, and patients who initiate pemetrexed and platinum-based chemotherapy alone.

Enrollment

851 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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
Prior diagnosis of interstitial lung disease or diagnosis of pneumonitis and record of treatment with glucocorticoids within 30 days