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296 Background: Enzalutamide (E) and abiraterone acetate with prednisone (AAP) are approved for treatment (tx) of metastatic castration resistant prostate cancer (mCRPC). Concerns of differences in CNS manifestations and tolerability between E and AAP have been reported. REAAcT evaluated tolerability in patients (pts) newly starting E and AAP for mCRPC. Methods: This was a multicenter, Phase IV, non-randomized, prospective real-world study (NCT02663193). The tx (E or AAP) determined by the treating physician was prescribed per USPI. PROs (EORTC QLQ 30, FACIT-Fatigue, FACT-Cog) and tests of 4 cognitive domains (Cogstate) were assessed at baseline (BL) and after 2 months (M2) tx and analyzed for evaluable pts who completed BL and M2 assessments with no major protocol deviations. Descriptive statistics were provided. BL Cogstate scores were used to estimate the rate of cognitive impairment defined as ≥2SD from age-matched normative means of healthy males on ≥2 tests. Reliable change index (RCI) was calculated. Pts were noted to have clinically meaningful cognitive change with a performance decline of |RCI|≥2 on ≥2 tests. Results: Of 100 pts treated, 92 pts were evaluable (E = 46 and AAP = 46). Median age was 75 years. At BL, characteristics and median scores were similar between arms, with mild cognitive impairment in ~20% of pts. Drug discontinuations due to AEs were similar (1 vs. 2 pts), but more dose reductions due to AEs occurred on E vs. AAP (16% vs. 6%). Overall, more AEs were reported on E vs. AAP (52% vs. 36%), but Grade 3/4 AEs (4% E vs. 6% AAP) were similar. Unique neuropsychiatric AEs on E included amnesia, cognitive disorders, memory impairment, and confusional state; on AAP: cerebrovascular accident, presyncope, and spinal cord compression. Regarding fatigue, more AEs were noted on E than AAP (26% vs. 8%) and showed greater worsening in E than AAP (median change -4 vs. 0) by FACIT-Fatigue. This change within E group was statistically significant (mean, 95% CI -4 (-6.61, -1.39)). Four pts on E and 1 pt on AAP had clinically meaningful cognitive decline. Conclusions: While baseline values were similar between arms, after 2 months of tx, differences of fatigue and neurocognition were noted more often with E than AAP. Clinical trial information: NCT02663193.

Background Androgen deprivation therapy (ADT), a cornerstone of prostate cancer treatment, is commonly co-prescribed as combination therapy. Objective To better understand the safety and tolerability profile of relugolix, an oral non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, in combination with abiraterone acetate (abiraterone) and apalutamide, a phase I study was undertaken. Patients and Methods This is an ongoing, 52-week, open-label, parallel cohort study of relugolix in combination with abiraterone in men with metastatic castration-sensitive prostate cancer (mCSPC) or metastatic castration-resistant prostate cancer (mCRPC) [Part 1] and apalutamide in men with mCSPC or non-metastatic castration-resistant prostate cancer (nmCRPC) [Part 2]. Eligible patients treated with leuprolide acetate or degarelix with abiraterone or apalutamide prior to baseline, at which time they were transitioned to relugolix. Assessments included reporting of adverse events, clinical laboratory tests, vital sign measurements, electrocardiogram (ECG) parameters, and testosterone serum concentrations. In this interim report, patients completing ≥12 weeks were included. Results Overall, 15 men were enrolled in Part 1 and 10 in Part 2. Adverse events were mostly mild-to-moderate in intensity and were consistent with the known safety profiles of the individual medications. No transition (from prior ADT treatment)-or time-related trends in clinical laboratory tests, vital sign measurements, or ECG parameters were observed. Mean testosterone concentrations remained below castration levels. Conclusions Combination therapy of relugolix and abiraterone or apalutamide was associated with a favorable safety and tolerability profile consistent with the known profiles of the individual medications. Castration levels of testosterone were maintained after transitioning to relugolix from other ADTs.