Incidence and Risk Factors of Pneumonitis in Patients with Non-Small Cell Lung Cancer: An Observational Analysis of Real-World Data.

ABSTRACT

INTRODUCTION: The incidence of pneumonitis, a treatment-related adverse event (AE) in non-small cell lung cancer (NSCLC) patients, has been studied in the United States mostly through clinical trials and retrospective chart reviews. Few analyses of real-world data have been published. This study of a large nationally representative health records database estimated the incidence and predictors of pneumonitis among treated NSCLC patients between 2008 and 2018. METHODS: The Optum® electronic health records (EHR) database includes data on over 80 million patients from more than 50 healthcare plans. The cohort of primary NSCLC patients was identified using ICD-9/10 codes. Natural language processing of unstructured data from physicians' notes facilitated extraction of biomarker (epidermal growth factor receptor [EGFR] and programmed death ligand-1 [PD-L1]) status. Cumulative incidence was estimated as the proportion with pneumonitis overall, by clinical characteristics, and line of therapy (LOT) after diagnosis and treatment. Univariate analysis of incidence rates (cases/1000 person-years) enabled the identification of significant predictors of risk. Competing risk regression identified predictors of pneumonitis. RESULTS: The cohort included 81,628 patients. Overall, 19.0% developed pneumonitis during any LOT, with a cumulative incidence of 33.7% and 17.0% for patients with a prior history of pneumonitis and those without, respectively. Univariate analyses revealed several factors associated with pneumonitis (p < 0.05). While factors varied between LOTs, common factors included male gender, squamous histology, history of diabetes or pneumonitis, EGFR-negative status, monotherapy immunomodulatory drugs, or history of radiation therapy. Multivariable competing risk regression showed that male gender, history of pneumonitis, EGFR-negative status, use of other targeted therapies, use of immunomodulatory drugs, and history of radiation therapy predicted pneumonitis. CONCLUSION: Pneumonitis is significantly associated with NSCLC treatment. Knowledge of its predictors identified in this study may help devise strategies to mitigate its impact, enhancing treatment adherence and improving outcomes.

Pneumonitis is a side effect of non-small cell lung cancer (NSCLC) treatment. Real-world data on its incidence in the United States is not extensive. In this study, the Optum® electronic health records database with data on over 80 million patients from more than 50 healthcare plans across the United States was used to estimate the incidence and predictors of pneumonitis in NSCLC patients treated between 2008 and 2018. A total of 81,628 NSCLC patients were identified using disease-specific codes. Physicians' notes in their health records were subjected to natural language processing to identify presence of epidermal growth factor receptor (EGFR) and programmed death ligand-1 (PD-L1) receptors in tumors. Proportions of patients with pneumonitis overall, by clinical characteristics, and line of therapy (LOT) were calculated. Univariate analysis of incidence (cases per 1000 person-years) a multivariable competing risk regression helped identify risk predictors. Overall, 19.0% of patients developed pneumonitis during any LOT. Incidence was 33.7% and 17.0% in patients with and without prior pneumonitis, respectively. Univariate analysis revealed factors associated with pneumonitis, including male gender, squamous histology, history of diabetes or pneumonitis, EGFR-negative status, monotherapy immunomodulatory drugs, or history of radiation therapy. Multivariable competing risks regression analysis showed that male gender, history of pneumonitis, EGFR-negative status, use of other targeted therapies, use of immunomodulatory drugs, and history of radiation therapy were significantly associated with pneumonitis. Pneumonitis is significantly associated with NSCLC treatment. Knowledge of its predictors may help design interventions to lessen its impact, promoting compliance with treatment and improving outcomes.