A First-Time Comparison Reveals the Efficacy of Abiraterone Acetate Compared With Enzalutamide in Prostate Cancer

A First-Time Comparison Reveals the Efficacy of Abiraterone Acetate Compared With Enzalutamide in Prostate Cancer

The initiation of enzalutamide (Xtandi) when compared with abiraterone acetate (Zytiga), presented small but statistically significant improvements in overall survival (OS), prostate cancer-specific survival (PCS), time to next treatment switching or death (TTS), and time to prostate-specific antigen (PSA) response (TTR) in patients with metastatic castration-resistant prostate cancer, according to results from a study published in JAMA Network Open.

“The findings of this large-scale observational study with robust follow-up and rigorous methods may provide guidance for making well-informed decisions about mCRPC treatment strategies,” the study authors wrote.

A median follow-up of 38 months to 60 months revealed longer average OS with enzalutamide compared with abiraterone acetate, with restricted mean survival times (RMSTs) of 24.29 months (95% CI, 23.58–24.99) and 23.38 months (95% CI, 22.85–23.92 months), respectively. At 4 years, the difference in RMST between both groups was 0.90 months (95% CI, 0.02-1.79).

Additionally, results demonstrated improved TTS and TTR in patients treated with enzalutamide. RMST at 4 years for patients treated with enzalutamide was 1.95 months (95% CI, 0.92–2.99) longer for TTS and 3.57 months (95% CI, 1.76–5.38) shorter for TTR. Patients in the enzalutamide group had an RMST at 2 years that was 0.48 months (95% CI, 0.01–0.95) longer than those in the abiraterone acetate group.

During the trial, researchers analyzed data by subgroups and identified that enzalutamide initiation was associated with longer RMST in OS in patients who did not previously receive docetaxel (1.14 months; 95% CI, 0.19-2.10) and in those with a PSA doubling time of 3 months or longer (2.23 months; 95% CI, 0.81-3.66 months). This was not seen in patients who previously received docetaxel (−0.25 months; 95% CI, −2.59 to 2.09) and a PSA doubling time of less than 3 months (0.05 months; 95% CI, −1.05 to 1.15).

The purpose of this study was to compare clinical outcomes of patients with metastatic castration-resistant prostate cancer who were treated with abiraterone acetate or enzalutamide. To do so, researchers analyzed data from a large, retrospective cohort of patients in the US Department of Veterans Affairs health care system between January 1, 2014, and October 30, 2022.

The study included 5779 patients with mCRPC (median age, 74.42 years) who started treatment with abiraterone acetate or enzalutamide.

“Compared with previous retrospective studies, this study provided more information on mCRPC treatment options by investigating a larger cohort with more recent data, observing follow-up of patients for a longer duration with a comprehensive set of outcomes, and applying more rigorous methods,” study authors wrote.

To control for potential confounders, inverse probability of treatment weighting was used. This controlled for potential confounders such as age, race/ethnicity, comorbidities, frailty, treatment initiation year, prior treatment, baseline PSA level, and PSA doubling time.

Abiraterone acetate and enzalutamide are often used as first-line treatment of mCRPC. “Abiraterone acetate intensifies testosterone suppression and works upstream in the pathway, whereas enzalutamide blocks multiple downstream events, including [androgen receptor] nuclear translocation and transcription,” study authors wrote.

Researchers assessed several outcomes in this study including OS, PCS, TTR, and TTS.

Limitations of this study included absence of potential cofounders that were not available within the data (i.e., tumor volume, Gleason score) and the US veteran population having an overall high burden of comorbidity.

Reference

La J, Wang L, Corrigan JK, et al. Abiraterone or Enzalutamide for Patients With Metastatic Castration-Resistant Prostate Cancer. JAMA Netw Open. 2024;7(8):e2428444. Published 2024 Aug 1. doi:10.1001/jamanetworkopen.2024.28444