Systemic therapies for high-volume metastatic hormone-sensitive prostate cancer: a network meta-analysis

Abstract

Background: We compared the effectiveness of currently available systemic therapies for high-volume metastatic hormone-sensitive prostate cancer (mHSPC) and aimed to establish the optimal treatment regimen. Material and Methods: We searched multiple databases for randomized controlled trials (RCTs) that evaluated the efficacy of systemic therapy in patients with high-volume mHSPC. Bayesian network meta-analysis was used to indirectly compare overall survival (OS) and progression-free survival (PFS) of various systemic therapies. Results: Eleven RCTs (6708 participants) finally met the eligibility criteria. Compared with androgen deprivation therapy (ADT) alone, rezvilutamide (REZ) [hazard ratio (HR) = 0.58, 95% confidence interval (CI): 0.44–0.77], abiraterone (ABI) (HR = 0.61, 95% CI: 0.53–0.71), apalutamide (APA) (HR = 0.70, 95% CI: 0.56–0.88), enzalutamide (ENZ) (HR = 0.65, 95% CI: 0.53–0.80), docetaxel (DOC) (HR = 0.72, 95% CI: 0.63–0.84), darolutamide (DAR) + DOC (HR = 0.49, 95% CI: 0.39–0.62), and ABI + DOC (HR = 0.52, 95% CI: 0.38–0.71) significantly improved OS in patients with high-volume mHSPC. Compared with DOC, no advantages were observed for doublet therapies, including REZ, ABI, APA, and ENZ on the basis of ADT, whereas DAR + DOC (HR = 0.68, 95% CI: 0.57–0.82) and ABI + DOC (HR = 0.72, 95% CI: 0.55–0.95) was associated with better OS. The ranking analysis showed that triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT) had the greatest improvement in OS, followed by REZ + ADT. All the regimens showed improved PFS in patients with high-volume mHSPC. Compared with DOC, significant differences were detected for DAR + DOC, ABI + DOC, ENZ + DOC, REZ, and ENZ. According to the ranking analysis, triplet therapy ranked first, followed by ENZ and REZ. Conclusions: REZ + ADT were the highest ranked doublet therapy for improvement in OS of patients with high-volume mHSPC, second only to triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT).