Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States.

BACKGROUND: Incidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer. METHODS: The Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2-/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates. RESULTS: 27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35-12.33) and 201.3 (95% CI: 198.05-204.50), respectively, per 100 person-years. HER2-/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). With HER2-/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low. CONCLUSIONS: This study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients' tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.

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

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.

Cumulative incidence of post-infection asthma or wheezing among young children clinically diagnosed with respiratory syncytial virus infection in the United States: A retrospective database analysis.

BACKGROUND: Respiratory syncytial virus (RSV) infection is implicated in subsequent development of asthma/wheezing (AW) among term and pre-term infants. We describe the cumulative incidence of AW among hospitalized and ambulatory neonates/infants/toddlers following RSV infection diagnosis over three independent follow-up periods. METHODS: Between January 1, 2007 and March 31, 2016, patients aged 0-2 years old with first clinical diagnosis of RSV infection were identified using the Optum® integrated electronic health records and claims database. Patients diagnosed with AW ≤ 30 days post-RSV diagnosis were excluded. Three cohorts with 1, 3, and 5 years of follow-up were stratified by presence or absence of specific RSV high-risk factors, including pre-term birth and pre-defined, pre-existing comorbidities. Descriptive statistics and logistic regression results were reported. RESULTS: Overall, 9811, 4524, and 1788 RSV-infected high-risk factor negative patients were included in 1, 3, and 5-year independent cohorts, respectively. Of these, 6.5%, 6.9%, and 5.8%, respectively had RSV-related hospitalization. By the end of follow-up, 14.9%, 28.2%, and 36.3% had AW events. Overall, 3030, 1378, and 552 RSV-infected high-risk factor positive patients were included in the respective cohorts. Of these, 11.4%, 11.1%, and 11.6%, respectively were hospitalized with initial RSV infection and 18.1%, 32.9%, and 37.9% had subsequent AW events within the follow-up period. Logistic regression confirmed RSV-related hospitalization significantly increased the likelihood of developing AW (P < .05) in high-risk factor positive and negative patients. CONCLUSIONS: In infants diagnosed with RSV infection, RSV-related hospitalization was associated with a significantly increased likelihood of AW development for at least 5 years, compared with non-hospitalized patients.