care initiative: real-world emulation of the keynote-189 trial [ds3]

Conditions: Metastatic Nonsmall Cell Lung Cancer

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?

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.

Eligibility criteria:
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 \&gt;=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

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