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Comparative Study
. 2024 Aug 1;7(8):e2428444.
doi: 10.1001/jamanetworkopen.2024.28444.

Abiraterone or Enzalutamide for Patients With Metastatic Castration-Resistant Prostate Cancer

Jennifer La  1   2 , Lin Wang  3 , June K Corrigan  1 , Deborah Lang  4 , Michelle H Lee  2   5 , Nhan V Do  1   6 , Mary T Brophy  1   7 , Channing J Paller  1   8 , Nathanael R Fillmore  1   2   9
Affiliations
Comparative Study

Abiraterone or Enzalutamide for Patients With Metastatic Castration-Resistant Prostate Cancer

Jennifer La et al. JAMA Netw Open. .

Abstract

Importance: Abiraterone acetate and enzalutamide are recommended as preferred treatments for metastatic castration-resistant prostate cancer (mCRPC), but differences in their relative efficacy are unclear due to a lack of head-to-head clinical trials. Clear guidance is needed for making informed mCRPC therapeutic choices.

Objective: To compare clinical outcomes in patients with mCRPC treated with abiraterone acetate or enzalutamide.

Design, setting, and participants: This retrospective, multicenter cohort study included patients with mCRPC in the US Department of Veterans Affairs health care system who initiated treatment with abiraterone acetate or enzalutamide between January 1, 2014, and October 30, 2022.

Exposures: Abiraterone acetate or enzalutamide.

Main outcomes and measures: The study used inverse probability of treatment weighting to balance baseline characteristics between patients initiating abiraterone acetate or enzalutamide and evaluated restricted mean survival time (RMST) differences 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) at different time points after treatment initiation.

Results: The study included 5779 patients (median age, 74.42 years [IQR, 68.94-82.14 years]). Median follow-up was between 38 and 60 months. Patients initiating enzalutamide on average had longer OS than those initiating abiraterone acetate, with RMSTs of 24.29 months (95% CI, 23.58-24.99 months) and 23.38 months (95% CI, 22.85-23.92 months), respectively, and a difference in RMST of 0.90 months (95% CI, 0.02-1.79 months) at 4 years. Similarly, TTS and TTR were improved in patients initiating enzalutamide, with an RMST at 4 years of 1.95 months (95% CI, 0.92-2.99 months) longer for TTS and 3.57 months (95% CI, 1.76-5.38 months) shorter for TTR. For PCS, the RMST at 2 years was 0.48 months (95% CI, 0.01-0.95 months) longer. An examination of subgroups identified that enzalutamide initiation was associated with longer RMST in OS among patients without prior docetaxel treatment (1.14 months; 95% CI, 0.19-2.10 months) and in those with PSA doubling time of 3 months or longer (2.23 months; 95% CI, 0.81-3.66 months) but not among patients with prior docetaxel (-0.25 months; 95% CI, -2.59 to 2.09 months) or with PSA doubling time of less than 3 months (0.05 months; 95% CI, -1.05 to 1.15 months).

Conclusions and relevance: In this cohort study of patients with mCRPC, initiation of enzalutamide was associated with small but statistically significant improvements in OS, PCS, TTS, and TTR compared with initiation of abiraterone acetate. The improvements were more prominent in short-term outcomes, including TTS and TTR, and in patient subgroups without prior docetaxel or with PSA doubling time longer than 3 months.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr La reported receiving a grant from Merck during the conduct of the study. Dr Wang reported employment with Bristol-Myers Squibb but conducted the research for the study separate from that employment. Dr Paller reported consulting for Janssen, Bayer, and Pfizer and conducting clinical research with Merck and AstraZeneca. Dr Fillmore reported receiving a grant from Merck outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram Depicting Selection of Study Cohort
NLP indicates natural language processing; PSA, prostate-specific antigen.
Figure 2.
Figure 2.. Outcomes in Patients Initially Treated With Abiraterone Acetate vs Enzalutamide After Inverse Probability of Treatment Weighting
Kaplan-Meier plots and the difference in restricted mean survival time (RMST) at each time point (3-month increments) are shown. The RMST at a given time point measures the mean survival censoring at the time point and is equal to the area under the Kaplan-Meier plot up to the time point. PSA indicates prostate-specific antigen.
Figure 3.
Figure 3.. Differences in Restricted Mean Survival Time (RMST) at 4 Years After Treatment Initiation for the Full Cohort and for Subgroups Defined by Prostate-Specific Antigen Doubling Time (PSADT) and Prior Receipt of Docetaxel
See this image and copyright information in PMC

References

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