Efficacy and safety of triple or dual therapies for metastatic hormone-sensitive prostate cancer: a systematic review and Bayesian network meta-analysis
Creators: name: Jiang, Jingqi
name: Wang, Yuhan
name: Bai, Jiangtao
name: Yang, Gaoyang
name: Wang, Hanzhang
name: Ding, Hui
name: Zhang, Yunxin
name: Zhai, Zhenxing
name: Dong, Zhilong
name: Wang, Zhiping
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Science Policy
subject: Infectious Diseases
subject: FOS: Health sciences

description: <b>Aim:</b> To compare triple and dual therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). <b>Methods:</b> A Bayesian network meta-analysis was conducted to indirectly compare overall survival, progression-free survival and adverse events in mHSPC patients with triple and dual therapies. <b>Results:</b> Triple and dual therapies were related to considerably higher overall survival than androgen-deprivation therapy (ADT), and darolutamide + docetaxel + ADT (hazard ratio [HR]: 0.54; 95% CI: 0.39–0.76; P score = 0.89) emerged as the best option. In terms of progression-free survival, abiraterone + prednisolone + docetaxel + ADT (HR: 0.33; 95% CI: 0.19–0.53; P score = 0.92) emerged as the best option. Apalutamide + ADT had the lowest odds of adverse events. <b>Conclusion:</b> Triple therapies were particularly effective in mHSPC patients, but the incidence of adverse events was significantly high. A network meta-analysis was used to indirectly compare overall survival, progression-free survival and adverse events in metastatic hormone-sensitive prostate cancer patients receiving triple and dual therapies. Triple therapies have shown significant benefits but their safety should be closely monitored. The phase III PEACE-1 (NCT01957436) and ARASENS (NCT02799602) trials combined novel androgen signaling inhibitors with chemotherapeutics to treat metastatic hormone-sensitive prostate cancer (mHSPC) and showed long-term survival benefits. The phase III trials CHART (NCT03520478) combined the novel endocrine drug rezvilutamide (SHR3680) also recently released the latest data. Rezvilutamide plus androgen deprivation therapy (ADT) significantly improved radiological progression-free survival and overall survival compared with high-volume mHSPC patients with a tolerable safety profile. Here, network meta-analyses were applied to compare not only which treatment strategy was more advantageous between triple and dual therapies, but also within triple and dual therapies, as well as between novel androgen inhibitors and chemotherapeutic drugs. The majority of phase III clinical trials were controlled by ADT, so ADT was selected as the primary reference therapy for efficacy and safety. According to the published results of phase III clinical trials, overall survival and progression-free survival were selected as the main outcomes to judge the efficacy of each regimen. Clinical safety outcomes included all grades of adverse events and ≥3 grade adverse events. To increase the credibility of the network meta-analysis results, high- and low-volume subgroup and sensitivity analyses were carried out. In the network meta-analysis results, triple therapies were particularly effective in mHSPC patients, but the incidence of adverse effects was significantly increased. Rezvilutamide + ADT significantly improved the survival benefit of patients in the high-volume subgroup. Apalutamide+ ADT had the lowest incidence of adverse effects among all modalities and may be the most effective for low-volume mHSPC patients.