■第二代雄激素受体抑制剂(SGARIs),即恩杂鲁胺,阿帕鲁胺,还有达鲁鲁胺,有利于改善前列腺癌患者的生存结果,但是一些研究人员表明,使用SGARIs会增加副作用,这使得临床医生的选择变得复杂。因此,我们进行了这项网络荟萃分析,以评估几种SGARIs治疗转移性激素敏感性前列腺癌(mHSPC)患者的疗效和毒性,非转移性去势耐药前列腺癌(nmCRPC),和转移性去势耐药前列腺癌(mCRPC)。
■我们搜索了PubMed,2000年1月至2022年12月EMBASE和Cochrane图书馆数据库,以确定与SGARIs相关的随机对照研究。我们使用Stata16.0和R4.4.2进行数据分析,风险比(HR)和95%置信区间(CI)用于评估结果.
■这项荟萃分析包括7项研究,共9488名患者。在mHSPC中,恩杂鲁胺和达洛鲁胺对总生存期(OS)有积极影响(HR,0.70;95%CI,0.59-0.82),但我们没有发现它们在提高操作系统(HR,1.19;95%CI,0.75-1.89)。同样在nmCRPC中,恩扎鲁他胺,阿帕鲁胺和达洛鲁胺对无转移生存期(MFS)有益(HR,0.32;95%CI,0.25-0.41)。与达鲁鲁胺相比,恩扎鲁他胺(HR,0.71;95%CI,0.54-0.93)和阿帕鲁胺(HR,0.68;95%CI,0.51-0.91)延长MFS,但是恩杂鲁胺和阿帕鲁胺之间的疗效没有差异(HR,0.97;95%CI,0.73-1.28)。最后在mCRPC中,恩杂鲁胺化疗前后对OS的间接影响没有显着差异(HR,0.89;95%CI,0.70-1.13)。然而,在化疗前使用恩杂鲁胺改善放射学无进展生存期(rPFS)是更好的选择(HR,2.11;95%CI,1.62-2.73)。
■每个试验中使用的SGARIs对研究的主要终点是有益的。首先,恩杂鲁胺和达洛鲁胺在改善mHSPC患者OS方面的作用没有显着差异。其次,恩杂鲁胺和阿帕鲁他胺最好改善nmCRPC患者的MFS。此外,在mCRPC患者中,化疗前后使用恩杂鲁胺对OS均有益。但为了改善rPFS,化疗前使用恩杂鲁胺应该是优选的.本系统评价的INPLASY注册号为INPLASY202310084。
Second-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer patients, but some researchers have shown that using SGARIs increases side effects, which complicates clinicians\' choice of. Therefore, we performed this network meta-analysis to assess the efficacy and toxicity of several SGARIs in the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC).
We searched PubMed, EMBASE and Cochrane Library databases from January 2000 to December 2022 to identify randomized controlled studies associated with SGARIs. We use Stata 16.0 and R 4.4.2 for data analysis, hazard ratio (HR) with 95% confidence intervals (CI) were used to assess the results.
This meta-analysis included 7 studies with a total of 9488 patients. In mHSPC, enzalutamide and darolutamide had a positive effect on overall survival (OS) (HR, 0.70; 95% CI, 0.59-0.82), but we did not find a difference in their efficacy to improve OS (HR, 1.19; 95% CI, 0.75-1.89). Also in nmCRPC, enzalutamide, apalutamide and darolutamide were beneficial for metastasis-free survival (MFS) (HR, 0.32; 95% CI, 0.25-0.41). Compared to darolutamide, enzalutamide (HR, 0.71; 95% CI, 0.54-0.93) and apalutamide (HR, 0.68; 95% CI, 0.51-0.91) prolonged MFS, but there was no difference in efficacy between enzalutamide and apalutamide (HR, 0.97; 95% CI, 0.73-1.28). Finally in mCRPC, there was no significant difference in indirect effects on OS between pre- and post-chemotherapy enzalutamide (HR, 0.89; 95% CI, 0.70-1.13). However, using enzalutamide before chemotherapy to improve radiographic progression-free survival (rPFS) was a better option (HR, 2.11; 95% CI, 1.62-2.73).
The SGARIs used in each trial were beneficial for the primary endpoint in the study. Firstly there was no significant difference in the effect of enzalutamide and darolutamide in improving OS in patients with mHSPC. Secondly improving MFS in patients with nmCRPC was best achieved with enzalutamide and apalutamide. In addition both pre- and post-chemotherapy use of enzalutamide was beneficial for OS in mCRPC patients, but for improving rPFS pre-chemotherapy use of enzalutamide should be preferred.The INPLASY registration number of this systematic
review is INPLASY202310084.