CARE Initiative: Real-world Emulation of the KEYNOTE-189 Trial [DS4]

Completed

• Conditions: Metastatic Non Small Cell Lung Cancer
• Interventions: Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

• Registration Number: NCT06585189
• Lead Sponsor: Aetion, Inc.

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

Detailed 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.

Study Timeline

• Study Start: 2010-02-01
• Primary Completion: 2023-04-13
• Study Completion: 2023-04-13
• Status Verified: 2024-09
• Study First Submitted: 2024-09-03
• Study First Submitted QC: 2024-09-03
• Last Update Submitted: 2024-09-03
• Study First Posted: 2024-09-05
• Last Update Posted: 2024-09-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 304

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

• Receipt of an investigational agent or device in the 4 weeks before study drug initiation

  • 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 rheumatic disease in the 2 years prior to study drug initiation
  • Prior treatment with pembrolizumab or any other anti-PD-1, PD-L1, PDL2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms
  • Diagnosis of human immunodeficiency virus infection

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Exposed	Cisplatin	Patients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC
Comparator	Carboplatin	Patients initiating pemetrexed and cisplatin or carboplatin as first-line treatment for metastatic NSCLC
Exposed	Pembrolizumab	Patients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC
Exposed	Pemetrexed	Patients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC
Exposed	Carboplatin	Patients initiating pemetrexed, cisplatin or carboplatin, and pembrolizumab as first-line treatment for metastatic NSCLC
Comparator	Pemetrexed	Patients initiating pemetrexed and cisplatin or carboplatin as first-line treatment for metastatic NSCLC
Comparator	Cisplatin	Patients initiating pemetrexed and cisplatin or carboplatin as first-line treatment for metastatic NSCLC

Primary Outcome Measures

Name	Time	Method
Real-world overall survival (rwOS)	Study treatment initiation to death or censoring	Time from study treatment initiation to death
Real-world progression-free survival (rwPFS)	Study treatment initiation to disease progression, death, or censoring	Time from study treatment initiation to disease progression or death