We perform an updated systematic review and network meta-analysis of randomized control trials that evaluated systemic therapies in men with castration-sensitive prostate cancer. We searched multiple databases up to April 2022. We included all randomized trials assessing the effect of systemic agents. We performed subgroup analyses based on disease volume and timing of presentation. Statistical analysis was performed with Bayesian methods.
We found 10 eligible trials with 10,065 patients who were included in this analysis. Triplet therapy with darolutamide or abiraterone with docetaxel and ADT improved overall survival. In the sensitivity analysis, the respective hazard ratios for triplet therapy was HR 0.70 (95%CI 0.61-0.80) compared to docetaxel+ADT and 0.77 (95%CI 0.65-0.91) compared to androgen receptor pathway inhibitors+ADT combinations. It was estimated that there was 96% chance that one of the triplet therapy combinations were the best treatment option from an OS perspective. Triplet therapy also improved progression-free survival. These benefits were pronounced in men with high-volume disease burden and those with de novo metastatic disease.
The finding suggest that triplet therapy is likely the most efficacious available option in men with metastatic, castration-sensitive prostate cancer, especially in those with high-volume disease burden.
方法:我们对评价男性去势敏感前列腺癌患者的全身治疗的随机对照试验进行了更新的系统评价和网络荟萃分析。截至2022年4月,我们搜索了多个数据库。我们纳入了所有评估全身药物效果的随机试验。我们根据疾病体积和出现时间进行了亚组分析。采用贝叶斯方法进行统计分析。
结果:我们发现了10项符合条件的试验,10,065名患者被纳入本分析。达洛鲁胺或阿比特龙联合多西他赛和ADT的三联疗法可改善总生存率。在敏感性分析中,与多西他赛+ADT相比,三联疗法的风险比分别为HR0.70(95CI0.61~0.80),与雄激素受体途径抑制剂+ADT组合相比,风险比分别为0.77(95CI0.65~0.91).据估计,从OS的角度来看,三联疗法组合之一是最佳治疗选择的可能性为96%。三联疗法还改善了无进展生存期。这些益处在患有大量疾病负担的男性和患有从头转移性疾病的男性中明显。
结论:该发现表明,三联疗法可能是转移性男性患者最有效的选择。对去势敏感的前列腺癌,尤其是那些有大量疾病负担的人。