Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies

详细信息    查看全文

• 作者：Joaquim Bellmunt^a ; ^{Joaquim_Bellmunt@dfci.harvard.edu" class="auth_mail" title="E-mail the corresponding author} ; Thian Kheoh^b ; Margaret K. Yu^c ; Matthew R. Smith^d ; Eric J. Small^e ; Peter F.A. Mulders^f ; Karim Fizazi^g ; Dana E. Rathkopf^h ; Fred Saadⁱ ; Howard I. Scher^h ; Mary-Ellen Taplin^a ; Ian D. Davis^j ; Dirk Schrijvers^k ; Andrew Protheroe^l ; Arturo Molina^m ; Peter De Porreⁿ ; Thomas W. Griffin^c ; Johann S. de Bono^o ; Charles J. Ryan^e ; Sté ; phane Oudard^p
• 关键词：Abiraterone acetate ; Androgen receptor antagonists ; Gonadotropin-releasing hormone ; Prednisone ; Prostate cancer
• 刊名：European Urology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：69
• 期：5
• 页码：924-932
• 全文大小：1032 K

文摘

The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

Objective

To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity.

Design, setting, and participants

Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-naïve mCRPC (COU-AA-302) patients receiving AA. The treatment effect on overall survival (OS), radiographic progression-free survival (rPFS), and prostate-specific antigen (PSA) response analysed by quartile duration of prior gonadotropin-releasing hormone agonists (GnRHa) or androgen receptor (AR) antagonist.

Intervention

Patients were randomised to AA (1000 mg, orally once daily) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone. Prior endocrine therapy was GnRHa (COU-AA-301, n = 1127 [94%]; COU-AA-302, n = 1057 [97%], 45.1 mo or 36.7 mo median duration, respectively) and/or orchiectomy (COU-AA-301, n = 78 [7%] COU-AA-302, n = 44 [4%]); castrated patients received prior AR antagonists (COU-AA-301, n = 1015 [85%]; COU-AA-302, n = 1078 [99%], 15.7 mo or 16.1 mo median duration, respectively).

Outcome measurements and statistical analysis

Cox model was used to obtain hazard ratio and associated 95% confidence interval with statistical inference by log rank statistic.

Results and limitations

Clinical benefit with AA was observed for OS, rPFS, and PSA response for nearly all quartiles with GnRHa or AR antagonists in both COU-AA-301 and COU-AA-302. In COU-AA-301, patients with a longer duration of prior endocrine therapy tended to have greater AA OS, rPFS, and PSA response benefit, with lead-time chemotherapy bias potentially impacting COU-AA-301 results. Time to castration resistance was not captured. This analysis is limited as a post-hoc exploratory analysis.

Conclusions

In the COU-AA-301 and COU-AA-302 studies, AA produced clinical benefits regardless of prior endocrine therapy duration in patients with mCRPC.

Patient summary

Metastatic castration-resistant prostate cancer patients derived clinical benefits with abiraterone acetate regardless of prior endocrine therapy duration.