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. 2020 Sep 18:10:519388.
doi: 10.3389/fonc.2020.519388. eCollection 2020.

Comparison of Current Systemic Combination Therapies for Metastatic Hormone-Sensitive Prostate Cancer and Selection of Candidates for Optimal Treatment: A Systematic Review and Bayesian Network Meta-Analysis

Junru Chen  1 , Yuchao Ni  1 , Guangxi Sun  1 , Banghua Liao  1 , Xingming Zhang  1 , Jinge Zhao  1 , Sha Zhu  1 , Zhipeng Wang  1 , Pengfei Shen  1 , Hao Zeng  1
Affiliations

Comparison of Current Systemic Combination Therapies for Metastatic Hormone-Sensitive Prostate Cancer and Selection of Candidates for Optimal Treatment: A Systematic Review and Bayesian Network Meta-Analysis

Junru Chen et al. Front Oncol. .

Abstract

Objective: To compare the efficacy and safety of current systemic combination therapies for patients with mHSPC and help select candidates for optimal treatment. Methods: Databases of MEDLINE and EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trial.gov were searched for eligible studies. Direct and network meta-analysis were conducted to compare various systemic combination therapies and the surface under the cumulative ranking curve (SUCRA) was generated for treatment ranking. Subgroup analyses were performed according to the extent of metastasis. Adverse events (AEs) were compared among the effective treatments. Results: Ten trials with 16 publications were included in this network meta-analysis. Direct and network meta-analysis consistently suggested that androgen-deprivation therapy (ADT) combined with docetaxel, abiraterone, enzalutamide, or apalutamide could significantly improve overall survival (OS) and failure-free survival (FFS) compared to ADT alone in men with mHSPC. SUCRA analysis demonstrated the superiority of ADT plus abiraterone or enzalutamide over other therapies. Subgroup analyses indicated that additional abiraterone to ADT had the highest ranking in patients with high-volume diseases or visceral metastases and enzalutamide plus ADT outperformed other treatments in patients with low-volume diseases or without visceral metastases. Different combination therapies had variable AE profiles and ADT in addition with docetaxel or abiraterone had the highest risk of AEs. Conclusion: ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide were associated with significantly improved survival in patients with mHSPC. ADT plus abiraterone or enzalutamide appeared to be the most effective treatments. Clinicians should balance the efficacy, potential AEs, and disease status to select the optimal treatment.

Keywords: androgen-deprivation therapy; chemotherapy; combination therapy; metastatic prostate cancer; network meta-analysis.

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Figures

Figure 1
Figure 1
PRISMA flowchart of study selection.
Figure 2
Figure 2
Forest plots of direct comparisons. (A) Effect of combination therapies compared to ADT alone on overall survival. (B) Effect of ADT plus abiraterone compared to ADT plus docetaxel on overall survival. (C) Effect of combination therapies compared to ADT alone on failure-free survival. (D) Effect of ADT plus abiraterone compared to ADT plus docetaxel on failure-free survival. Doc, docetaxel; Abi, abiraterone; Enza, enzalutamide; Apa, apalutamide; Bis, bisphosphonate; Cel, celecoxib; ADT, androgen-deprivation therapy.
Figure 3
Figure 3
Network comparisons of effect of systemic therapies on overall survival (yellow) and failure-free survival (blue). Results are the HRs with 95% CrIs from the network meta-analysis between the row intervention and column intervention. Doc, docetaxel; Abi, abiraterone; Enza, enzalutamide; Apa, apalutamide; Bis, bisphosphonate; Cel, celecoxib; ADT, androgen-deprivation therapy.
Figure 4
Figure 4
Forest plots of network comparisons of effect of combination therapies compared to ADT alone on overall survival (A) and failure-free survival (B). Rankings are presented as probabilities of ranking first and SUCRA. Doc, docetaxel; Abi, abiraterone; Enza, enzalutamide; Apa, apalutamide; ADT, androgen-deprivation therapy.
Figure 5
Figure 5
Ranking probabilities of effective therapies for overall survival and failure-free survival. (A) Ranking probabilities of effective therapies for overall survival in patients with high-volume diseases. (B) Ranking probabilities of effective therapies for failure-free survival in patients with high-volume diseases. (C) Ranking probabilities of effective therapies for overall survival in patients with low-volume diseases. (D) Ranking probabilities of effective therapies for failure-free survival in patients with low-volume diseases. (E) Ranking probabilities of effective therapies for overall survival in patients with visceral metastases. (F) Ranking probabilities of effective therapies for failure-free survival in patients with visceral metastases. (G) Ranking probabilities of effective therapies for overall survival in patients without visceral metastases. (H) Ranking probabilities of effective therapies for failure-free survival in patients without visceral metastases. Doc, docetaxel; Abi, abiraterone; Enza, enzalutamide; Apa, apalutamide; ADT, androgen-deprivation therapy.
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