Neil M Schultz1, David F Penson2, Samuel Wilson3, Yan Song4, Hongbo Yang4, Krishnan Ramaswamy5, Benjamin Lowentritt6. 1. Astellas Pharma Inc., 1 Astellas Way, Northbrook, IL, 60062, USA. neil.schultz@astellas.com. 2. Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA. 3. Astellas Pharma Inc., 1 Astellas Way, Northbrook, IL, 60062, USA. 4. Analysis Group, Inc., 111 Huntington Avenue, Floor 14, Boston, MA, 02199, USA. 5. Pfizer Inc., 235 E. 42nd Street, New York, NY, 10017, USA. 6. Chesapeake Urology, 6535 N. Charles Street, Suite 500, Towson, MD, 21204, USA.
Abstract
INTRODUCTION: Corticosteroids are a mainstay treatment for castration-resistant prostate cancer (CRPC). Although corticosteroids have been associated with adverse events, long-term outcomes related to their sustained use have not been assessed in men with CRPC. OBJECTIVE: This study evaluated the impact of cumulative corticosteroid exposure on the risk of developing specific adverse events in men with CRPC. METHODS: Data were obtained from administrative claims databases. Adult chemotherapy-naïve men who initiated CRPC treatment following surgical or medical castration were selected. Patients were grouped into four cohorts based on cumulative corticosteroid dose: no exposure, low exposure (< 0.5 g), medium exposure (0.5-2.0 g), and high exposure (> 2.0 g). Time to each adverse event was assessed using Kaplan-Meier analyses and time-dependent Cox proportional hazard models, adjusting for baseline characteristics. RESULTS: Overall, 9425 patients were included (no exposure, N = 6765; low exposure, N = 1660; medium exposure, N = 655; high exposure, N = 345). The mean age was 71-76 years across cohorts. During the study period, cumulative corticosteroid exposure was associated with a significantly higher risk of developing an infection [high vs. no exposure, adjusted hazard ratio (HR) 2.55; 95% confidence interval (CI) 2.27-2.85; p < 0.001 for trend], peptic ulcer (HR 1.91; 95% CI 1.39-2.64; p < 0.001), acute cardiovascular events (HR 1.62; 95% CI 1.43-1.83; p < 0.001), endocrine disorder (HR 1.61; 95% CI 1.34-1.94; p < 0.001), fracture (HR 1.59; 95% CI 1.37-1.86; p < 0.001), or mental health condition (HR 1.28; 95% CI 1.06-1.55; p = 0.014). Exposure to corticosteroids was associated with a more rapid onset of adverse events. CONCLUSION: Patients with CRPC receiving corticosteroids had a higher risk of developing a wide range of adverse events than those not receiving them. The increased adverse event risk was observed after accounting, to the extent possible, for patients' overall disease severity.
INTRODUCTION: Corticosteroids are a mainstay treatment for castration-resistant prostate cancer (CRPC). Although corticosteroids have been associated with adverse events, long-term outcomes related to their sustained use have not been assessed in men with CRPC. OBJECTIVE: This study evaluated the impact of cumulative corticosteroid exposure on the risk of developing specific adverse events in men with CRPC. METHODS: Data were obtained from administrative claims databases. Adult chemotherapy-naïve men who initiated CRPC treatment following surgical or medical castration were selected. Patients were grouped into four cohorts based on cumulative corticosteroid dose: no exposure, low exposure (< 0.5 g), medium exposure (0.5-2.0 g), and high exposure (> 2.0 g). Time to each adverse event was assessed using Kaplan-Meier analyses and time-dependent Cox proportional hazard models, adjusting for baseline characteristics. RESULTS: Overall, 9425 patients were included (no exposure, N = 6765; low exposure, N = 1660; medium exposure, N = 655; high exposure, N = 345). The mean age was 71-76 years across cohorts. During the study period, cumulative corticosteroid exposure was associated with a significantly higher risk of developing an infection [high vs. no exposure, adjusted hazard ratio (HR) 2.55; 95% confidence interval (CI) 2.27-2.85; p < 0.001 for trend], peptic ulcer (HR 1.91; 95% CI 1.39-2.64; p < 0.001), acute cardiovascular events (HR 1.62; 95% CI 1.43-1.83; p < 0.001), endocrine disorder (HR 1.61; 95% CI 1.34-1.94; p < 0.001), fracture (HR 1.59; 95% CI 1.37-1.86; p < 0.001), or mental health condition (HR 1.28; 95% CI 1.06-1.55; p = 0.014). Exposure to corticosteroids was associated with a more rapid onset of adverse events. CONCLUSION:Patients with CRPC receiving corticosteroids had a higher risk of developing a wide range of adverse events than those not receiving them. The increased adverse event risk was observed after accounting, to the extent possible, for patients' overall disease severity.
Authors: Dora Liu; Alexandra Ahmet; Leanne Ward; Preetha Krishnamoorthy; Efrem D Mandelcorn; Richard Leigh; Jacques P Brown; Albert Cohen; Harold Kim Journal: Allergy Asthma Clin Immunol Date: 2013-08-15 Impact factor: 3.406
Authors: Jimmy L Zhao; Karim Fizazi; Fred Saad; Kim N Chi; Mary-Ellen Taplin; Cora N Sternberg; Andrew J Armstrong; Johann S de Bono; William T Duggan; Howard I Scher Journal: Clin Cancer Res Date: 2022-03-01 Impact factor: 13.801