Association of intermittent vs continuous androgen deprivation therapy with cardiovascular disease and endocrine/metabolic disorders in patients with metastatic prostate cancer.

Abstract

82 Background: There is mixed evidence on the risks of cardiovascular disease (CVD) and endocrine/metabolic disorders associated with long-term intermittent and continuous androgen deprivation therapy (iADT and cADT, respectively) for metastatic prostate cancer (mPC). This study examined these risks in patients (pts) with mPC receiving iADT vs cADT in the US. Methods: This was a retrospective cohort study of SEER-Medicare pts with mPC initiating ADT (2010–2017), with ≥36 months of continuous insurance coverage, unless death occurred, who did not receive chemotherapy or a second-generation anti-androgen during follow-up. iADT and cADT cohorts were defined by treatment patterns and gaps in therapy. Comorbidities and clinical events were identified using ICD-9/10-CM codes. Outcomes examined were major adverse cardiovascular events (MACE [myocardial infarction (MI), stroke, cardiomyopathy/heart failure (HF), pulmonary embolism (PE), ischemic heart disease (IHD), or all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, or osteoporosis). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between cohorts; weighted Cox models were used to estimate the hazard ratio (HR) of the outcomes. Subgroup analyses examined pts by CVD history; a sensitivity analysis was performed restricting the definition of MACE to include CVD-related mortality as a component, i.e., MACESA (MI, stroke, cardiomyopathy/HF, PE, IHD, or CVD-related mortality). Results: 2234 pts with mPC were included; 478 (21%) received iADT and 1756 (79%) cADT. Median follow-up time was 27 and 13 months, and time on ADT (excluding gaps for iADT pts) was 24 and 19 months for the iADT and cADT cohorts, respectively. Deaths occurred in 39% of iADT pts vs 55% of cADT pts; PC was the most common cause of death in both cohorts. In adjusted analyses, pts receiving cADT had a higher risk of MACE vs iADT. No differences in risk of endocrine/metabolic events were observed. Subgroup analysis showed that baseline history of CVD did not alter the results for MACE. Sensitivity analysis results showed no difference in risk of MACESA between pts receiving cADT vs iADT. Conclusions: Pts with mPC receiving cADT had a higher risk of MACE (including all-cause mortality), and no difference in risk of endocrine/metabolic events, compared with those receiving iADT. When MACE was restricted to include CVD-related mortality, there was no difference in risk between cohorts. [Table: see text]