Darolutamide Favorably Affects Episodic Memory Vs Enzalutamide in mCRPC

Treatment with darolutamide (Nubeqa) was associated with statistically significant benefits in episodic memory by computerized cognitive assessment compared with enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to findings from the prospective phase 2 ODEZA trial (NCT03314324) that were presented in a poster at the 2021 ESMO Congress.¹

Favorable effects of darolutamide resulted in better verbal learning and verbal memory compared with enzalutamide, with nonsignificant trends towards executive function also noted.

“The favorable effect of darolutamide on episodic memory over enzaluamide was observed for both the acquisition of new information, as well as for the recall of that information after a brief delay,” the authors of the poster, who were led by Emeline Colomba, MD, of the Department of Cancer Medicine at Institut Gustave Roussy of University of Paris Saclay in Villejuif, France, wrote.

Low blood-brain barrier penetrance is a known benefit of darolutamide vs other antiandrogen agents, such as enzalutamide. Results of the ODENZA trial that were previously reported at the 2021 American Society of Clinical Oncology Annual Meeting indicated that numerically more patients reported preferring darolutamide than enzalutamide, although these correlations did not reach statistical significance. Of note, fatigue was a key influencing factor for preference and was reported in 21% of patients receiving darolutamide vs 36% with enzalutamide.²

Patients with mCRPC (n = 249) were randomized 1:1 to either darolutamide at 1200 mg daily for 12 weeks followed by enzalutamide at 160 mg daily for 12 weeks or the reverse sequence. The current assessment looks at cognitive assessment, a key secondary end point of the study, using computerized tests to determine changes from baseline during each 12-week period.

Criteria for evaluation included detection test (DET) for psychomotor function and an identification test (IDT) for visual attention, which comprised an attention composite score; a working memory, or One Back Test (OBT), and an executive function, or Groton Maze Learning test (GML), which comprised an executive function composite score; and a verbal learning, or International Shopping List test (ISL), and a verbal memory testing, or International Shopping List test–delayed recall (ISRL), comprising a memory composite (episodic memory) score.

Cognitive data were available in 193 patients in total. Effects sizes were considered clinically meaningful at 0.5 or greater.

The memory composite score demonstrated a statistically significant benefit of darolutamide (P <.001), with a least square (LS) mean difference of 0.35 and an effect size of 0.54. Performance on verbal learning by ISL were significantly improved with darolutamide and effects were clinically meaningful, both at the second period (0.62; P = .0001) and overall (0.54; P < .0001). Performance on verbal learning was also better with darolutamide at the second period (0.4; P = .01) and overall (0.29; P = .0075), although these effects were less clinically meaningful.

Between darolutamide and enzalutamide, the effect sizes for both the executive function and attention composite scores were 0.15, with LS mean differences of 0.09 and 0.12, respectively (P = not significant).

Overall, investigators noted that composite scores were in line with individual scores and that moderate benefit with darolutamide was noted for episodic memory.

References

1. Colomba E, Jonas SF, Yymard J-C, et al. Objective computerized cognitive assessment in men with metastatic castrate-resistant prostate cancer (mCRPC) randomly receiving darolutamide or enzalutamide in the ODENZA trial. Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021. Virtual. Abstract 603P.
2. Colomba E, Jonas SF, Yymard J-C, et al. ODENZA: A French prospective, randomized, open-label, multicenter, cross-over phase II trial of preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (CRPC). J Clin Oncol. 2021;39(suppl 15):5046. doi:10.1200/JCO.2021.39.15_suppl.5046