Emulation of the KEYNOTE-042 (NCT02220894) Trial Using Specialty Oncology Electronic Health Records Databases

Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Study Period: ENCORE database 1 (EDB1): Patient identification period: 01/01/2011-04/30/2024 with follow-up information through data cut-off date on 04/30/2024 ENCORE database 2 (EDB2): Follow-up information through February 2023 (there is no specific time period restrictions for patient eligibility) ENCORE database 4 (EDB4): Patient identification period: 10/01/2018-09/30/2023 with follow-up information through data cut-off date on 09/30/2023. Inclusion Criteria: * Age ≥18 years at treatment initiation * Subjects with histologically or cytologically confirmed advanced or metastatic NSCLC that is not amenable to curative-intent treatment * ECOG 0 or 1 * Line of therapy setting classified as "advanced" (EDB1) or "metastatic" (EDB2), or evidence of metastatic disease at treatment initiation (EDB4) * PD-L1 ≥ 50% Exclusion Criteria: * Patients with documentation of prior chemotherapy administration for advanced/metastatic NSCLC * Pembrolizumab group: patients with documented EGFR/ALK positivity * Chemotherapy group: patients with documented EGFR/ALK positivity or missing/unknown EGFR/ALK status * Missing/unknown or PD-L1 \< 50% * Patients with any documentation of an investigational agent within 4 weeks prior to initiation of first-line pembrolizumab/chemotherapy * Squamous patients with any documentation of prior carboplatin plus paclitaxel * Patients with any documentation of chemotherapy or biologic therapy within 3 weeks prior to initiation of first-line pembrolizumab/chemotherapy * Patients with documentation of prior immunotherapy administration * Patients with any prior non-lung malignancy diagnosis (exceptions: basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer) * Patients with documented autoimmune diseases within 2 years prior to treatment initiation * Patients with documented interstitial lung disease * Patients with documented CNS metastases