OBJECTIVES: The androgen receptor inhibitors (ARI) enzalutamide, apalutamide, and darolutamide have been recommended for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). With the publication of the final analysis of the overall survival of the patients in the three main randomized controlled trials that evaluated these drugs, a systematic analysis of their benefits and risks is once again necessary. The aim of this study is to conduct a meta-analysis of the efficacy and safety of ARIs for the treatment of nmCRPC.

METHODS: A direct meta-analysis was conducted to evaluate the efficacy and safety of the ARIs for the treatment of nmCRPC. An indirect meta-analysis was conducted to compare the drugs against each other. The results of the random-effects model adjusted by the DerSimonian and Laird method were presented. All analyses were conducted in R.

RESULTS: The ARIs were considered efficacious in terms of overall survival (HR=0.74, 95%CI=0.65-0.83), metastasis-free survival (HR=0.32, IC95%=0.25-0.41), and PSA progression-free survival (HR=0.09, IC95%=0.06-0.13). They were, though, associated with an increased incidence of serious adverse events (RR=1.21, IC95%=1.07-1.37) and GRADE 3 or 4 adverse events (HR=1.31, IC95%=1.18-1.45). The network meta-analysis showed no difference between the drugs in terms of overall survival, but metastasis-free survival and PSA progression-free survival were significantly higher with apalutamide and enzalutamide than with darolutamide. No difference between the drugs in terms of the serious or GRADE 3 and 4 adverse events was observed.

CONCLUSIONS: The ARIs are efficacious and relatively safe for the treatment of nmCRPC. The three drugs are similar in terms of efficacy and safety with minor differences in intermediate outcomes.