Sequential therapy of abiraterone and enzalutamide in castration-resistant prostate cancer: a systematic review and meta-analysis,Prostate Cancer and Prostatic Diseases

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Sequential therapy of abiraterone and enzalutamide in castration-resistant prostate cancer: a systematic review and meta-analysis
Prostate Cancer and Prostatic Diseases ( IF 5.1 ) Pub Date : 2020-03-09 , DOI: 10.1038/s41391-020-0222-6
Keiichiro Mori _{1,

2} , Noriyoshi Miura _{1,

3} , Hadi Mostafaei _{1,

4} , Fahad Quhal _{1,

5} , Reza Sari Motlagh ₁ , Benjamin Pradere _{1,

6} , Shoji Kimura _{1,

2} , Takahiro Kimura ₂ , Shin Egawa ₂ , Alberto Briganti ₇ , Pierre I Karakiewicz ₈ , Shahrokh F Shariat _{1,

9,

10,

11,

12,

13,

14,

15}

Affiliation

Department of Urology, Medical University of Vienna, Vienna, Austria.
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Urology, Ehime University Graduate School of Medicine, Ehime, Japan.
Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Department of Urology, CHRU Tours, Francois Rabelais University, Tours, France.
Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada.
Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Department of Urology, Weill Cornell Medical College, New York, NY, USA.
Department of Urology, University of Texas Southwestern, Dallas, TX, USA.
Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.
Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Urology, University of Jordan, Amman, Jordan.
European Association of Urology Research Foundation, Arnhem, Netherlands.

Background

This systematic review and meta-analysis aimed to assess the prognostic value of sequential of abiraterone (ABI) and enzalutamide (ENZ) therapy in patients with castration-resistant prostate cancer (CRPC).

Methods

PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched for articles published prior to December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared overall survival (OS), combined progression-free survival (PFS), combined prostate specific antigen (PSA)-PFS, and PSA response rates in CRPC patients receiving sequential ABI/ENZ or vice versa. PSA response to both the first and second agents was defined as a >50% decrease in PSA achieved with each of these agents. Formal meta-analyses were performed for these outcomes.

Results

Ten studies with 1096 patients were eligible for the systematic review and eight studies with 643 patients for the meta-analysis. The ABI-to-ENZ sequence was significantly associated with better PFS (pooled hazard ratio (HR): 0.62, 95% confidential interval (CI): 0.49–0.78, P < 0.001), and PSA–PFS (pooled HR: 0.48, 95% CI: 0.38–0.61, P < 0.001) than the ENZ-to-ABI sequence. PSA response rates of both agents were significantly better with the ABI-to-ENZ sequence (risk ratio: 0.21, 95% CI: 0.09–0.47, P < 0.001). In contrast, treatment sequence was not significantly associated with OS (pooled HR: 0.77, 95% CI: 0.59–1.01, P = 0.055).

Conclusions

ABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS, PSA–PFS, and PSA response rates. Regardless of sequencing, response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy. Despite this, treatment sequencing is important to achieve the maximum possible benefit from available drugs in CRPC.

中文翻译：

阿比特龙和恩杂鲁胺在去势抵抗性前列腺癌中的序贯治疗：系统评价和荟萃分析

背景

本系统评价和荟萃分析旨在评估阿比特龙 (ABI) 和恩杂鲁胺 (ENZ) 序贯治疗对去势抵抗性前列腺癌 (CRPC) 患者的预后价值。

方法

根据系统评价和 Meta 分析声明的首选报告项目，在 PUBMED、Web of Science、Cochrane 图书馆和 Scopus 数据库中搜索了 2019 年 12 月之前发表的文章。如果研究比较了接受序贯 ABI/ENZ 的 CRPC 患者的总生存期 (OS)、联合无进展生存期 (PFS)、联合前列腺特异性抗原 (PSA)-PFS 和 PSA 反应率，则被认为符合条件，反之亦然。对第一种和第二种药物的 PSA 反应定义为使用这些药物中的每一种实现的 PSA 降低 >50%。对这些结果进行了正式的荟萃分析。

结果

10 项涉及 1096 名患者的研究符合系统评价条件，8 项研究涉及 643 名患者进行荟萃分析。ABI-to-ENZ 序列与更好的 PFS（汇总风险比 (HR)：0.62，95% 机密区间 (CI)：0.49-0.78，P < 0.001）和 PSA-PFS（汇总 HR：0.48， 95% CI: 0.38–0.61, P < 0.001) 比 ENZ-to-ABI 序列。ABI-to-ENZ 序列的两种药物的 PSA 反应率明显更好（风险比：0.21，95% CI：0.09-0.47，P < 0.001）。相比之下，治疗顺序与 OS 没有显着相关性（汇总 HR：0.77，95% CI：0.59–1.01，P = 0.055）。