Androgen receptor axis-targeted agents for non-metastatic castration-resistant prostate cancer impact on overall survival and safety profile

Keiichiro Mori, Fahad Quhal, Satoshi Katayama, Hadi Mostafaei, Ekaterina Laukhtina, Victor M. Schuettfort, Reza Sari Motlagh, Nico C. Grossmann, Pawel Rajwa, Guillaume Ploussard, Alberto Briganti, Takahiro Kimura, Shin Egawa, Rocco Papalia, Diego M. Carrion, Cristian Fiori, Shahrokh F. Shariat, Francesco Esperto, Benjamin Pradere

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)


inTrodUCTion: The management of non-metastatic castration-resistant prostate cancer (nmCrpC) has undergone a paradigm shift with the development of androgen receptor axis-targeted (ARAT) agents. The updated results with final overall survival (oS) data of the phase iii proSper, SparTan, and araMiS trials have recently been reported. Therefore, we performed an updated meta-analysis and network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. evidenCe aCQUiSiTion: Multiple databases were searched for articles published before January 2021. Studies that compared oS and adverse events (aes) in patients with nmCrpC were considered eligible. evidenCe SynTheSiS: Three studies (n.=4117) met our eligibility criteria. Formal network meta-analyses were conducted. ARAT agent is associated with significantly longer OS compared to placebo (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001), with similar results shown for patients with both N1 and N0 disease (pooled hr 0.61 and pooled hr 0.76, respectively). in the network meta-analysis, apalutamide, darolutamide, and enzalutamide were more effective than placebo, with similar efficacies in terms of OS. For AEs (including any AEs, grade 3 or grade 4 aes, grade 5 aes, serious aes, and aes leading to treatment discontinuation), darolutamide was shown to be likely well tolerated. Quality of life was preserved in treatment arms irrespective of the drug. CONCLUSIONS: All three ARAT agents are efficacious options for the treatment of nmCRPC, whereas darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.

Original languageEnglish
Pages (from-to)292-301
Number of pages10
JournalMinerva Urology and Nephrology
Issue number3
Publication statusPublished - Jun 2022


  • Apalutamide
  • Castration
  • Darolutamide
  • Enzalutamide
  • Network meta-analysis
  • Prostatic neoplasms

ASJC Scopus subject areas

  • Nephrology
  • Urology


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