Among treatments for nonmetastatic castration-resistant prostate cancer (nmCRPC), darolutamide may provide the best overall survival (OS) benefit, whereas abiraterone may be the most cost-effective, according to new findings published in the Journal of the National Cancer Institute.

Citing an absence of head-to-head trials, G. Caleb Alexander, MD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and colleagues conducted a matching-adjusted indirect comparison and network meta-analysis of trials involving the androgen receptor inhibitors apalutamide, enzalutamide, and darolutamide and the androgen synthesis inhibitor abiraterone acetate for nmCRPC. The trials included a total of 4360 patients.

Darolutamide provided the largest OS benefit, the investigators reported. Compared with placebo, darolutamide, enzalutamide, and apalutamide were significantly associated with 31%, 27%, and 25% lower mortality risk, respectively.

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In addition, these 3 androgen receptor inhibitors and abiraterone prolonged the time to metastasis or death with the largest benefit observed for abiraterone. Metastasis-free survival (MFS) significantly improved by 78%, 72%, 70%, and 59% with abiraterone, apalutamide, enzalutamide, and darolutamide, respectively, compared with placebo. The investigators observed no MFS benefit with bicalutamide.  

All treatments increased serious adverse events (SAEs), however. Compared with placebo, darolutamide was associated with the lowest odds of SAE followed by enzalutamide, apalutamide, bicalutamide, and abiraterone at 32%, 43%, 58%, 63%, and 94%, respectively.

The investigators highlighted the cost differences among the drugs. The estimated 2-year treatment course cost was $34,378 for generic abiraterone acetate, $177,680 for enzalutamide, $190,314 for apalutamide, and $201,439 for darolutamide, according to the investigators.

“Our study has important implications for patients, clinicians, and payers, given the uncertainty about the risk/benefit balance of treatments for nmCRPC, as well as their highly variable costs,” Dr Alexander’s team stated. “Nevertheless, factors beyond those we examined also may inform treatment selection. For example, apalutamide and enzalutamide are associated with increased risks of seizure, ischemic heart disease, falls, and fractures, whereas darolutamide is not. Patients receiving abiraterone acetate plus prednisone need to be monitored for symptoms and signs of mineralocorticoid excess and adrenocortical insufficiency.”

Of note, included trials were subject to unblinding and crossover, which may undercut the benefits observed with these drugs.

Disclosure: This analysis was supported by Pharmaceutical Research and Manufacturers of America Foundation. Please see the original reference for a full list of authors’ disclosures.


Wang L, Paller C, Hong H, et al. Comparison of treatments for nonmetastatic castration-resistant prostate cancer: matching-adjusted indirect comparison and network meta-analysis. Published online April 8, 2021. J Natl Cancer Inst. doi:10.1093/jnci/djab071

This article originally appeared on Renal and Urology News