Medication patterns of abiraterone acetate plus prednisone or enzalutamide and PSA progression in veterans with metastatic castration-resistant prostate cancer

Abstract

Objectives To quantify the association between dose reductions of abiraterone acetate plus prednisone (AAP) or enzalutamide and prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC). Changes in medication-taking patterns of AAP or enzalutamide may arise due to clinical (e.g. toxicity) and non-clinical (e.g. patient compliance) reasons in men with mCRPC. However, it is unclear how this affects PSA progression. Methods Veterans Health Administration electronic health record database was used to identify Veterans diagnosed with prostate cancer who initiated AAP or enzalutamide (index) from April 2010 to December 2016. PSA progression was defined as the first rise in PSA of ≥2 ng/mL and ≥25% above nadir. The relative dose intensity (RDI) was defined as the ratio of the total dispensed dose over the last two months to the standard recommended dose and was updated monthly. Dose reduction was assessed using a threshold of RDI < 80%. Results The cohort included 6069 Veterans aged 74.6 years on average. Mean follow-up was 12.3 months. PSA progression occurred in 62.7% of patients. About 63.6% of AAP- and 67.2% of enzalutamide-treated patients had ≥1 occurrence of RDI <80%. RDI <80% was associated with an 8.8% higher risk of PSA progression (hazard ratio [HR] = 1.088; p = .019; 95% confidence interval [CI] [1.014; 1.166]). Conclusions Dose reduction was observed in most patients and was associated with significantly higher risk of PSA progression in men with mCRPC. These results suggest future efforts to minimize dose reductions for non-clinical reasons are warranted and that patient adherence should be encouraged to limit the risk of PSA progression.