Retrospective Study Reveals Enzalutamide Yields More Favorable Outcomes vs Abiraterone in mCRPC

Treatment with enzalutamide (Xtandi) was linked with 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) vs abiraterone acetate (Zytiga) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to findings from an observational study published in JAMA Network Open.¹

With a median follow-up ranging from 38 to 60 months, those who received enzalutamide (n = 2195) experienced longer OS on average than those who received abiraterone acetate (n = 3584), with respective 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) at 4 years, translating to a difference of 0.90 months (95% CI, 0.02-1.79).

Moreover, the RMST at 4 years in those who received enzalutamide was 1.95 months (95% CI, 0.92-2.99) longer with regard to TTS and 3.57 months (95% CI, 1.76-5.38) shorter with regard to TTR vs those who received abiraterone acetate. In terms of PCS, the RMST at 2 years was 0.48 months (95% CI, 0.01-0.95) longer with enzalutamide than abiraterone acetate.

Subgroup analysis revealed longer RMST in OS with enzalutamide vs abiraterone in those who had not previously received docetaxel (1.14 months; 95% CI, 0.19-2.10) and those who had a PSA doubling time of at least 3 months (2.23 months; 95% CI, 0.81-3.66); this was not the case for those who had prior docetaxel exposure (–0.25 months; 95% CI, –2.59 to 2.09) or those with a PSA doubling time under 3 months (0.05 months; 95% CI, –1.05 to 1.15).

“In this cohort study of patients with mCRPC, we found that initial enzalutamide treatment, in general, was associated with more favorable outcomes than initial abiraterone acetate treatment. The improvements were more prominent in short-term outcomes, including TTS and TTR, and in patient subgroups with less aggressive prostate cancer,” Jennifer La, PhD, of VA Cooperative Studies Program, VA Boston Healthcare System, in Boston, Massachusetts, and co-authors, wrote in the paper. “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.”

With the study, investigators set out to compare outcomes of patients with mCRPC who initiated treatment with enzalutamide vs abiraterone acetate between January 1, 2014, and October 30, 2022, by leveraging a large, retrospective cohort in the national US Department of Veterans Affairs (VA) health care system. Specifically, information on the patients was obtained from the VA Corporate Data Warehouse, which houses administrative and electronic health record data from US VA facilities.

“The study used inverse probability of treatment weighting to balance baseline characteristics between patients initiating abiraterone acetate or enzalutamide and evaluated RMST differences in OS, PCS, TTS, and TTR at different time points after treatment initiation,” the study authors wrote.

A total of 5779 patients met inclusion criteria. The median patient age in the cohort was 74.42 years (IQR, 68.94-82.14). Moreover, 61.0% of patients were White, 27.4% were Black, 6.2% were other or unknown race and ethnicity, and 5.4% were Hispanic. Before reweighting, those who received initial treatment with abiraterone were younger than those who received enzalutamide, had a higher likelihood of prior receipt of docetaxel and bisphosphonate and a lower likelihood of having comorbidities or prior exposure to radiation treatment. Those who received abiraterone were also noted to have a higher baseline median PSA level. Post reweighting, patient characteristics were noted to be well balanced.

Additional data indicated that in those who were initially treated with enzalutamide vs abiraterone, the RMST for OS was 0.27 months (95% CI, 0.11-0.43) longer at 1 year, 0.53 months (95% CI, 0.10-0.96) longer at 2 years, 0.78 months (95% CI, 0.10-1.46) longer at 3 years, and 0.90 months (95% CI, 0.02-1.79) longer at 4 years. For PCS, those who received enzalutamide vs abiraterone experienced 0.25 months (95% CI, 0.09-0.42) longer RMST at 1 year and 0.48 months (95% CI, 0.01-0.95) longer RMST at 2 years; no significant differences were observed in RMST at 3 years (0.62 months; 95% CI, –0.18 to 1.42) and 4 years (0.71 months; 95% CI, –0.43 to 1.84).

For TTS, the RMST was 0.60 months (95% CI, 0.37-0.82) longer with enzalutamide vs abiraterone at 1 year; the RMST was 1.21 months (95% CI, 0.69-1.74) and 1.72 months (95% CI, 0.93-2.51) longer at 2 and 3 years, respectively. For TTR, the RMST was 1.34 months (95% CI, 1.05-1.63) shorter at 1 year after initiation of enzalutamide vs abiraterone; the RMST was 2.10 months (95% CI, 1.42-2.78) shorter at 2 years and 2.93 months (95% CI, 1.67-4.19) shorter at 3 years.

The study was not without limitations. “Although we adjusted for many potential confounders using [inverse probability of treatment weighting], there are additional potential confounders that we were unable to include due to data availability, including diagnostic Gleason score, tumor volume, number and location of metastases, time since previous treatment, and duration of previous treatment,” the study authors concluded. “In addition, although we balanced the cohort across comorbidities, the US veteran population has an overall high burden of comorbidity, and results could differ in populations with less 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. doi:10.1001/jamanetworkopen.2024.28444