A Systematic Review And Network Meta-analysis Of The Effectiveness And Safety Of ADT Combination Therapy In Patients With MHSPC

Purpose:To conduct a systematic review and network meta-analysis(NMA)to compare the efficacy of currently available combination therapies in patients with metastatic hormone-sensitive prostate cancer(m HSPC).Methods:Qualified publications were searched in the Pub Med,Embase,and Cochrane CENTRAL databases.Overall survival(OS)and radiographic progression-free survival(r PFS)were indirectly compared and assessed using NMA and the surface under the cumulative ranking curve,respectively.Adverse events(AEs)were also compared.Results:Eighteen publications from 12 trials were analyzed in the NMA.In the overall population,triplet therapy was ranked first for OS(hazard ratio [HR]: 0.57,95%credible interval [Cr I]: 0.48–0.67)and r PFS(HR: 0.33,95% Cr I:0.26–0.41)compared with androgen deprivation therapy(ADT)with or without standard nonsteroidal antiandrogen.In high-volume m HSPC,triplet therapy was also ranked first in OS(HR,0.57;95% Cr I:0.44–0.75)and r PFS(HR,0.29;95% Cr I: 0.23–0.37).Specifically,abiraterone triplet therapy was ranked first in OS(HR,0.52;95% Cr I:0.38–0.72)and r PFS(HR,0.28;95% Cr I:0.21–0.38)among all therapies.ADT plus rezvilutamide was ranked first among doublet therapies(OS: HR,0.58;95% Cr I:0.44–0.77;r PFS:HR,0.44;95% Cr I:0.33–0.58).In low-volume m HSPC,doublet and triplet therapies were ranked first in OS(HR:0.68,95% Cr I:0.58–0.80)and r PFS(HR:0.37,95%Cr I:0.25–0.55),respectively.ADT plus apalutamide was ranked first in OS among all therapies(HR:0.53,95% Cr I:0.35–0.79),whereas enzalutamide triplet therapy was ranked first in r PFS(HR:0.27,95% Cr I:0.15–0.51).ADT plus rezvilutamide showed a relatively lower incidence of AE among all therapeis(OR:1.00,95% Cr I:0.31–3.15),and a lower risk of specific AEs among doublet therapies,particularly regarding seizure(OR,0.29;95% Cr I:0.01–8.18)and fatigue(OR,0.96;95% Cr I:0.63–1.46).Docetaxel-based doublet or triplet therapies significantly increased the risk of any AEs or grade ≥3 AEs.Conclusion:Triplet therapy was the best treatment option for the overall population.In high-volume m HSPC,triplet therapy and ADT plus rezvilutamide had the greatest potential to benefit patients.Patients with low-volume m HSPC were most likely to benefit from ADT plus androgen receptor-targeted agents.Triplet therapy was associated with a higher risk of AEs than the other therapies.