Assessment of central nervous system (CNS) and dose reduction events in patients treated with abiraterone acetate plus prednisone (AA+P) or enzalutamide (ENZ).

Abstract

5078 Background: The prognosis of patients with metastatic castrate resistant prostate cancer (PC) has improved with the availability of recent treatments such as AA+P or ENZ. However, concerns regarding adverse events such as CNS conditions, fatigue, and pain potentially leading to dose reductions or treatment interruption are rising. This study assessed CNS, fatigue, pain, and dose reduction events in AA+P or ENZ-treated patients. Methods: The MarketScan databases were used to conduct a retrospective analysis, in which patients initiated on AA+P or ENZ (index date) after 10/2012 with ≥ 6 months of continuous eligibility prior to index date and ≥ 1 PC diagnosis were included. Inverse probability of treatment weighting (IPTW) was used to adjust for observed baseline confounders between groups. Weighted Kaplan-Meier (KM) rates and Cox proportional hazard models were used to compare the occurrence of CNS, pain, fatigue, or dose reduction (i.e., relative dose intensity [RDI] ≤ 80%, and ≤ 85%) events between groups. CNS, pain, and fatigue events were assessed in patients without respective event at baseline. Results: A total of 2,196 AA+P and 807 ENZ patients were identified. IPTW resulted in balanced baseline demographic, comorbidities, and disease characteristics (AA+P = 1,493 and ENZ = 1,510). At 12 months, 30.3% of patients on AA+P had a CNS event compared to 37.5% of patients on ENZ (P = 0.005). Similarly, 25.0% of patients on AA+P had a fatigue event compared to 28.6% of patients on ENZ (P = 0.013). Respectively, 13.6% and 20.0% of AA+P and ENZ patients had a dose reduction event (RDI ≤ 80%, P < 0.001; Table). Conclusions: This national study showed that mCRPC patients treated with ENZ were more likely to experience a CNS or fatigue event, and to reduce their treatment dose than patients treated with AA+P. Event KM Rates HRs for Development of Event AA+P ENZ Log-Rank P-value ENZ vs. AA+P (95% CI) P-value CNS 30.3% 37.5% 0.005 1.32 (1.05, 1.66) 0.017 Fatigue 25.0% 28.6% 0.013 1.30 (1.02, 1.66) 0.033 Pain 12.9% 15.3% 0.267 1.17 (0.84, 1.63) 0.351 RDI ≤ 85% 19.4% 24.4% 0.006 1.29 (1.04, 1.61) 0.022 RDI ≤ 80% 13.6% 20.0% < .001 1.44 (1.11, 1.86) 0.006