Real-world study of enzalutamide and abiraterone acetate (with prednisone) tolerability (REAAcT): Results.

Abstract

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.

Comparing the clinical efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis

“…Two articles reported the risk for total CNS events. 15,24 Pilon et al. 15 reported that the rate of total CNS events was 7.3% with AA versus 9.1% with EnZ, and Shore et al.…”

“…Fourteen studies involving 3469 participants were included in the meta-analysis. 12–25 The characteristics of the eligible studies are presented in Table 1. The clinical outcomes of included studies are presented in Appendix 1.…”

“…Eight factors were used to assess study quality according to NOS. Included observational studies were of high quality, six studies 14–17,22,23 missed one indicator, six studies 13,18–21,24 missed two indicators. The results presented in Appendix 2 showed that all observational studies were of high quality.…”

“…15 reported that the rate of total CNS events was 7.3% with AA versus 9.1% with EnZ, and Shore et al. 24 reported that the rate was 36% with AA versus 52% with EnZ. Fatigue and perceived cognitive impairments were the most common CNS events affecting patients during treatment.…”

“…However, there are limited data comparing the clinical effectiveness of AA and EnZ. Recently, several new studies directly comparing AA with EnZ in mCRPC have been published, 12–25 and therefore, it is important and necessary to directly assess the efficacy and toxicity outcomes between AA and EnZ in mCRPC in real-world practice in order to produce an evidence-based recommendation for clinical practice.…”