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).

Keywords:

• Metastatic hormone-sensitive prostate cancer
• high-volume
• androgen receptor-targeted therapies
• chemotherapy
• triplet therapy

Authors’ contributions

G.Z.: Conceptualization, Data curation, Formal analysis, Investigation, Validation, Supervision; Z.Z.: Conceptualization, Investigation, Data Curation, Methodology, Writing—Original Draft, Project administration; S.L.: Investigation, Data Curation, Writing—Original Draft; J.M., T.L. and F.L.: Writing—Original Draft, Writing—Review and Editing, Supervision.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data is available upon request from corresponding author.

Additional information

Funding

This study was partly funded by the Natural Science Foundation of Shandong Province [ZR2021MH354], Medical and health research program of Qingdao [2021-WJZD170]. The funders had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript.