Purpose: The newly published ARASENS trial has demonstrated the clinical efficacy of darolutamide for metastatic hormone-sensitive prostate cancer (mHSPC). However, the use of darolutamide as the latest first-line androgen receptor pathway inhibitor for mHSPC has not been compared with other androgen receptor targeted agents (ARTAs). Given the lack of head-to-head randomized trials, we performed this updated meta-analysis to conduct indirect comparison for the efficacy and safety of darolutamide with other new-generation ARTAs.
Methods: By searching the databases of PubMed, Scopus, Cochrane Library, and Embase, 9 large randomized controlled trials evaluating ARTAs for mHSPC patients were eventually screened according to PRISMA. We extracted data from overall survival, castration-resistant progression, and adverse events for network meta-analysis using the Bayesian and standard frequentist models.
Results: Darolutamide combination emerged with superiority (HR = 0.68, 95%CrI = 0.57-0.81) among four androgen receptor inhibitors for patients with high Gleason score (HR = 0.71, 95%CrI = 0.59-0.86). Darolutamide was best tolerated in several androgen suppression-related adverse events (AEs).
Conclusion: Darolutamide appears to be an optional androgen receptor inhibitor for mHSPC patients, especially for patients with Gleason score ≥ 8. Its well-tolerated characteristic may provide a preferred drug option for patients with poor cardiovascular function and bone health.
Keywords: Androgen receptor targeted agents; Androgen suppression; Darolutamide; Network meta-analysis; mHSPC.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.