OBJECTIVES: To review the published literature on the efficacy and safety of licensed drugs and therapies currently in phase 3 development for the treatment of adults with non-metastatic (M0) castration-resistant prostate cancer (CRPC).

METHODS: A systematic literature review (SLR) of the clinical evidence was conducted in the PubMed and Cochrane databases, and the key relevant congress websites. No time-frame or geographic restrictions were applied.

RESULTS: Twelve publications reporting data from nine different studies were reviewed. The active interventions compared in these studies were apalutamide (SPARTAN trial), atrasentan (NCT00036556), bicalutamide plus dutasteride (TARP), darolutamide (ARAMIS), subcutaneous denosumab (NCT00286091), enzalutamide (PROSPER and STRIVE), poxviral vaccine (NCT00020254) and zibotentan (ENTHUSE 0). Atrasentan, dutasteride, poxviral vaccine and zibotentan appear to no longer be in clinical development for M0 CRPC due to the lack of efficacy in this setting. The ARAMIS, SPARTAN and PROSPER studies were still ongoing at the time of review. With the exception of STRIVE and NCT00286091, none of the other four completed studies demonstrated efficacy of the assessed interventions. In NCT00286091, denosumab significantly increased median metastasis-free survival versus placebo (29.5 versus 25.2 months). In STRIVE, enzalutamide significantly delayed disease progression of M0 CRPC patients with a hazard ratio versus bicalutamide of 0.24 (95% confidence interval 0.14, 0.42; p<0.001) for progression-free survival and a hazard ratio of 0.18 (95% confidence interval 0.10, 0.34; p<0.001) for time to prostate-specific antigen progression. However, STRIVE is a phase 2 study and M0 CRPC patients constituted only 35% of the total study population.

CONCLUSIONS: The SLR highlights the limited available evidence on treatment efficacy in the M0 CRPC setting. Ongoing clinical trials (ARAMIS, PROSPER, SPARTAN) may provide important evidence of clinical benefit in treating patients with M0 CRPC.