Results of a Real-world Study of Enzalutamide and Abiraterone Acetate with Prednisone Tolerability (REAAcT)

Abstract Objective To evaluate differences in tolerability in patients with mCRPC treated with enzalutamide (ENZA) or abiraterone acetate plus prednisone (AA+P). Methods This was a Phase IV, prospective, open-label, multicenter, real-world study. Patients were prescribed ENZA or AA+P at the treating physician’s discretion. Computerized tests of four cognitive domains (Cogstate), patient-reported outcomes (EORTC QLQ-30, FACIT-Fatigue, FACT-Cog), and patient/caregiver surveys were assessed at baseline and two months. Safety data were collected. Results Of 100 treated patients, 92 were evaluable (46/arm). Baseline characteristics were similar with mild cognitive impairment observed in ∼20% of patients. The FACIT-Fatigue demonstrated a statistically significant worsening from baseline of -4.00 (95% CI: -6.61, -1.39) for ENZA compared to AA+P, -0.01 (95% CI: -2.40, 2.38). Overall, more adverse events (AEs) and more AEs of fatigue were reported with ENZA vs. AA+P (52% vs. 36% and 26% vs. 8% respectively). Grade 3/4 AEs were similar (4% vs. 6%). Unique neuropsychiatric AEs reported with ENZA included amnesia, cognitive disorders, memory impairment, and confusional state; those for AA+P included cerebrovascular accident, presyncope, and spinal cord compression. Clinically meaningful cognitive decline was seen in four ENZA patients vs. one patient on AA+P. However, the overall mean changes from baseline for the Cogstate tests, the EORTC QLQ-C30, and the FACT-Cog assessment were similar and showed no meaningful change. Caregiver survey responses noted more fatigue with ENZA and more moodiness with AA+P compared with patient responses. Conclusions While baseline values were similar, more fatigue and neurocognitive differences were observed with ENZA compared with AA+P.