Though patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate or enzalutamide had comparable composite cognitive outcomes, patients treated with enzalutamide reported greater incidences of fatigue, depression, deterioration in perceived cognitive ability, and slower reaction time, according to results from the ACE study.

These results were presented by Amit Bahl, MBBS, MD, DNB, FRCP, FRCR, FFRRCSI, Bristol Haematology and Oncology Centre, United Kingdom, at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California.

“Abiraterone acetate and enzalutamide are both approved for the treatment of mCRPC [however] understanding the early impact of these treatments on various domains of cognitive function, depression and fatigue would lead to optimisation of treatment selection and promote supportive care planning in this patient group,” stated Dr Bahl and coauthors.

In this multi-center study, 253 patients with mCRPC were treated with either abiraterone acetate (n = 141) or enzalutamide (n = 112) followed by CATAB assessment at baseline, at 3-months (n = 184), 4-months, and 6-months (n = 131) to assess cognitive function and fatigue. Researchers additionally collected FACT-Cog, FACT-F, and PH9-Q questionnaires to assess patient-reported outcomes (PROs). 

At analysis, there were no performance differences in either treatment arm in terms of mean composite cognitive outcome (3-month P = .553; 6-month P = .198), the individual components for Spatial Working Memory, Rapid Information Processing, or Spatial Information Processing. However, outcomes for the Reaction Time Task were significantly different (3-month P =.009; 6-month P = .037). ANCOVA suggested that at 6 months, the gap between patients in the enzalutamide and abiraterone acetate arms significantly widened due to marginally poorer performance in the enzalutamide arm and marginally improved performance in the abiraterone acetate arm. 

Analysis of PROs at baseline and at each follow-up point revealed that patients in the enzalutamide arm experienced a significant deterioration in mean fatigue change (P < .001) compared to patients in the abiraterone acetate arm at 3-months (P < .001) and 6-months (P <.001). Mean PHQ-9 score showed increased levels of depression in both treatment arms, however patients in the enzalutamide arm experienced significantly poorer levels at 3-months (P  = .022) and 6-months (P  = .020). Mean PCA results and comments from others suggested that patients treated in the enzalutamide arm reacted significantly poorer at 3-months (P <.001) and at 6-months (P <.001) with no significant difference between groups in terms of perceived cognitive impairment. 

As Dr Bahl and coauthors concluded, “This is an important consideration for treatment optimisation and ensuring supportive strategies for the patients when using these drugs keeping in perspective the cognitive function assessment at baseline and subsequently on treatment.”

Source: 

Bahl A, Challapalli A, Birtle AJ, et al. Multi-centre prospective evaluation of cognitive function in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) or enzalutamide (ENZ): The ACE study. Presented at 2024 ASCO Gastrointestinal Cancer Symposium; January 25-27, 2024; San Francisco, California. Abstract 20