Real-world first-line osimertinib treatment in epidermal growth factor receptor mutation-positive (EGFRm) advanced NSCLC

Real-world evidence studies provide vital insight into treatment practices and outcomes beyond the clinical trial setting, reflecting the reality of healthcare systems. Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing (EGFRm) and EGFR T790M resistance mutations, and has demonstrated efficacy in EGFRm advanced non-small cell lung cancer (NSCLC), including central nervous system metastases. While osimertinib has demonstrated superior progression-free survival (PFS) and overall survival (OS) compared with first-generation EGFR-TKIs (erlotinib and gefitinib) as a first-line treatment in clinical trials, there remains a need to evaluate real-world disease characteristics and clinical outcomes of patients treated with first-line osimertinib monotherapy. This study aims to assess the long-term survival and treatment pathways after first-line osimertinib in patients with locally advanced/metastatic EGFRm NSCLC in a real-world setting.

This global, observational cohort study includes adult patients (≥18 years of age) diagnosed with advanced EGFRm NSCLC (stage IIIB–IV) or early stage disease (I–IIIA) that subsequently recurs or progresses, receiving first-line osimertinib monotherapy (initiating treatment between April 2018 and June 2021; initiation date range dependent on study country). Electronic health record (EHR) data from country-specific registries and hospital data provide de-identified information to characterise the patient population and understand treatment patterns and survival outcomes. These analyses will be conducted on each data source/geography separately and will not be pooled. Participating countries include USA (from the nationwide Flatiron Health de-identified EHR-derived database), Japan (chart review/EHRs), Germany (CRISP registry) and China (China Precision Medicine Lung Cancer Registry); data from other countries may be added later subject to availability of data and reimbursement status. Patient data will be extracted annually until June 2023, or until a median follow up of approximately 38 months is achieved; the cohort exit date will be defined as the earliest instance of either: the last day of available follow-up, date of death, or end of study period, whichever occurs first. The primary outcome measures are real-world OS and PFS (rwOS, rwPFS), treatment sequencing, and treatment dose and duration; second-line treatments after first-line osimertinib are included as part of the sequencing outcome. Baseline data will be assessed retrospectively from first date of NSCLC presentation until initiation of first-line osimertinib (index date). Patient characteristics at baseline and the incidence of brain metastases since baseline will be described using descriptive statistics; rwOS and rwPFS will be estimated using Kaplan-Meier methods, and the association between baseline characteristics and survival/progression outcomes will be examined using Cox proportional hazards models.

Conclusion: The characterisation of patients who receive first-line osimertinib monotherapy in the real world will provide further information on treatment patterns beyond the clinical trial setting, and describe the long-term survival and treatment pathways after first-line osimertinib.