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Translational Therapeutics

Efficacy and safety evaluation of androgen deprivation therapy-based combinations for metastatic castration-sensitive prostate cancer: a systematic review and network meta-analysis

British Journal of Cancer (2024)Cite this article

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Abstract

Background

This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC).

Methods

We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency.

Results

Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43–1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27–0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates.

Conclusions

Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients.

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Fig. 1: Literature search and selection.
Fig. 2: Comparative network plots for efficacy and toxicity of ADT-based combinations in different populations of patients with mCSPC according to the metastatic burden, metastatic presentation.
Fig. 3: Efficacy and safety profiles of the Bayesian network meta-analysis in overall patients with mCSPC.
Fig. 4: Safety profiles of ADT-based combinations.
Fig. 5: Bayesian ranking profiles for ADT-based combinations on efficacy and safety for patients with mCSPC.
Fig. 6: Forest plots of the subgroup analysis in patients with mCSPC according to metastatic burden and presentation.

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Data availability

Data used in this study are available in a public, open-access repository. All data relevant to the study are included in the Article or included in the Supplementary Materials.

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Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82370690, 82303813, 82073131), Natural Science Foundation of Shandong Province (Nos. ZR2023MH241, ZR2023QH271), and Taishan Scholars Programme of Shandong Province (Nos. tsqn201909199, tsqn202306403).

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Author notes

  1. These authors contributed equally: Tianqi Wang, Xiaoyu Wang.

Authors and Affiliations

  1. Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China

    Tianqi Wang, Guixin Ding, Hongquan Liu, Xiaohong Ma, Jian Ma, Yuanshan Cui & Jitao Wu

  2. Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China

    Xiaoyu Wang

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Contributions

WT and WX contributed to study conceptualisation, formal analysis, investigation, data curation, resource, statistical analysis, visualisation, and writing the original draft of the manuscript. DG contributed to formal analysis, investigation, statistical analysis, and writing, review, and editing of the manuscript. LH contributed to investigation, visualisation, and review and editing of the manuscript. MX and MJ contributed to investigation, data curation, and writing, review, and editing of the manuscript. CY contributed to investigation and writing, review, and editing of the manuscript. WJ contributed to conceptualisation, visualisation, supervision, and writing, review, and editing of the manuscript. All authors had access to and verified the data used in this study.

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Correspondence to Yuanshan Cui or Jitao Wu.

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Wang, T., Wang, X., Ding, G. et al. Efficacy and safety evaluation of androgen deprivation therapy-based combinations for metastatic castration-sensitive prostate cancer: a systematic review and network meta-analysis. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02823-3

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