Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration-resistant metastatic prostate cancer: A systematic review and meta-analysis

2021 ◽  
Vol 93 ◽  
pp. 102152
Author(s):  
J. Cassinello ◽  
T. Domínguez-Lubillo ◽  
M. Gómez-Barrera ◽  
T. Hernando ◽  
R. Parra ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
ZhenHeng Wei ◽  
ChuXin Chen ◽  
BoWen Li ◽  
YongYue Li ◽  
Hong Gu

ObjectiveThe androgen receptor-targeting drugs abiraterone acetate and enzalutamide have shown positive results as treatments for metastatic castration-resistant prostate cancer (mCRPC). Therefore, a meta-analysis was conducted to compare the efficacy and safety of abiraterone acetate and enzalutamide in patients with mCRPC.MethodsWe retrieved relevant articles from PubMed, Cochrane, and EMBASE published before December 31, 2020. Eleven articles were initially selected, and four phase III, double-blind, randomized controlled trials of abiraterone acetate and enzalutamide that involved 5199 patients with mCRPC were included. The end points were time to prostate-specific antigen progression (TTPP), according to the prostate-specific antigen working group criteria; overall survival (OS); and radiographic progression-free survival (rPFS).ResultsFour randomized, controlled clinical trials involving 5199 patients were included in this study. The results of the meta-analysis showed that compared with placebo alone, abiraterone significantly improved OS (HR=0.69, 95% CI: 0.60-0.8, P<0.00001), rPFS (HR=0.64, 95% CI: 0.57-0.71, P < 0.00001), and TTPP (HR=0.52, 95% CI: 0.45-0.59, P < 0.00001) in patients with mCRPC. Compared with placebo, enzalutamide significantly improved OS (HR=0.67, 95% CI: 0.59-0.75, P<0.00001), rPFS (HR=0.33, 95% CI: 0.29-0.37, P< 0.00001), and TTPP (HR=0.19, 95% CI: 0.17-0.22, P < 0.00001). An indirect comparison was performed to compare the efficacy of abiraterone and enzalutamide. The results showed that there was no significant difference between abiraterone and enzalutamide with regard to improving the OS of patients with mCRPC (HR=1.03, 95% CI: 0.854-1.242). Enzalutamide was superior to abiraterone with regard to improving rPFS in patients with mCRPC (HR=0.516, 95% CI: 0.438-0.608). With regard to improving TTPP, the efficacy of enzalutamide was better than that of abiraterone (HR=0.365, 95% CI: 0.303-0.441). In sAE, there was no difference between abiraterone and enzalutamide (P=0.21, I2 = 38%).ConclusionsCompared with placebo, both abiraterone and enzalutamide significantly prolonged OS, rPFS, and TTPP in patients with mCRPC. There was no difference in safety between abiraterone and enzalutamide. In addition, enzalutamide had better efficacy than abiraterone with regard to improving rPFS and TTPP but not OS, but the level of evidence was low. Therefore, a large direct comparison trial is needed to compare the efficacy of the two drugs.Systematic Review RegistrationPROSPERO, identifier (CRD42021226808)


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 43-43
Author(s):  
Gurudatta Naik ◽  
Charity Morgan ◽  
Pedro Filipe Simoes da Rocha ◽  
Arnoud J. Templeton ◽  
Gregory Russell Pond ◽  
...  

43 Background: Serum C-reactive protein (CRP), a marker of inflammation, appears to demonstrate a prognostic impact in small studies of metastatic prostate cancer (MPC). We conducted a meta-analysis to better quantitate its prognostic impact. Methods: A systematic review was conducted to identify publications and presentations exploring the association of baseline serum CRP and overall survival (OS) in MPC, both castration-sensitive and castration-resistant. The hazard ratio (HR) and 95% confidence interval (CI) with P values were pooled. HRs were selectively extracted from multivariable analyses. Estimates of HRs were weighted and pooled using the generic inverse variance and random-effect models. Heterogeneity among trials was assessed using Cochrane’s Q statistic and the I2 statistic was used to quantify inconsistency among trials. The assumption of homogeneity was considered invalid for P<0.1. All statistical tests were two-sided, and P<0.05 was considered significant Results: Six studies comprising 659 evaluable patients were eligible. The first authors were Prins (N=119), Pond (N=112), Ito (N=80), Nakashima (N=126), Beer (N=160), and McArdle (N=62). The Nakashima and McArdle studies evaluated castration-sensitive men, while the remaining four studies evaluated castration-resistant men receiving docetaxel-based chemotherapy. The primary endpoint was OS except the McArdle study, which used cancer specific survival. All HRs were derived from multivariate analyses except the Pond study, which was a bivariate analysis. Men with higher CRP had significantly worse OS than those with lower CRP (HR = 1.42, P<0.001, 95% CI: 1.17 to 1.73; I2 = 72.6%, p = 0.003). In trials of castration-sensitive men receiving hormonal therapy, high CRP yielded a HR = 1.92 (P=0.005, 95% CI: 1.22 to 3.03; I2 = 0). In castration-resistant men receiving chemotherapy, high CRP yielded HR=1.35 (p=0.003, 95% CI: 1.11 to 1.65; I2 = 79%), P for subgroup difference=0.20. Conclusions: This meta-analysis suggests a strong prognostic impact for CRP on OS in men with both castration-sensitive and castration-resistant prostate cancer. Prospective validation is justified, given the affordability, ready availability and large dynamic range of CRP.


Author(s):  
Abdilkerim Oyman ◽  
Mustafa Başak ◽  
Melike Özçelik ◽  
Deniz Tataroğlu Özyükseler ◽  
Selver Işık ◽  
...  

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