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Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases

Abstract

Background

Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions.

Methods

Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC.

Results

Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p < 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p < 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84–0.96).

Conclusions

Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases.

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Fig. 1: Kaplan-Meier plot of overall survival of all patients based on initial treatment with either enzalutamide or abiraterone.
Fig. 2: Kaplan-Meier plots of overall survival in subgroups of patients treated initially with enzalutamide or abiraterone for mCRPC with median months of survival reported.

Data availability

The dataset supporting the conclusions of this article will be shared upon request and execution of an agreement of use. Members of the scientific community can request a copy of the final dataset by e-mailing Dr. Martin Schoen at martin.schoen@va.gov. The investigator should state their reason for requesting the data and analysis plans. De-identified data will be provided after requestors sign a letter of agreement detailing the mechanisms by which the data will be kept secure and access restricted to their study team. The agreements will also state the recipient will not attempt to identify any individual whose data are included and will not share the data with anyone outside of their research team. Acknowledgement and attribution of scholarly effort is expected for any publication arising from shared data.

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Acknowledgements

We would like to thank Kelley Chadwick-Mansker for her efforts to shepherd this project and maintain compliance. We also appreciate the support of the VA St. Louis Health System Research and Development Service including Dr. Ziyad Al-Aly, Carolyn Williams and the St. Louis VA PREP Team including Amy Garner and Rebecca Kammer. This work was supported by a seed grant to Martin Schoen from the Saint Louis Veterans Affairs Medical Center.

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Concept and design: MWS, KRC, KMS, SAE, BFD, YY. Data Analysis SL and MWS. Initial drafting of the manuscript: MWS. Critical manuscript review and approval by all authors. MWS takes responsibility for all aspects of the work.

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Correspondence to Martin W. Schoen.

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All authors declare no competing financial interests or conflicts of interest related to this manuscript. Dr. Whitmer contributed to this work as an employee of the Saint Louis Veterans Affairs Medical Center prior to her joining Pfizer in 2022.

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Schoen, M.W., Carson, K.R., Eisen, S.A. et al. Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases. Prostate Cancer Prostatic Dis (2022). https://doi.org/10.1038/s41391-022-00588-5

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