Overall Survival Update for Patients with Metastatic Castration-resistant Prostate Cancer Treated with Capivasertib and Docetaxel in the Phase 2 ProCAID Clinical Trial

被引:27
作者
Crabb, Simon J. [1 ,2 ,6 ]
Griffiths, Gareth [1 ,2 ]
Dunkley, Denise [1 ,2 ]
Downs, Nichola [1 ,2 ]
Ellis, Mary [1 ,2 ]
Radford, Mike [1 ,2 ]
Light, Michelle [1 ,2 ]
Northey, Josh [1 ,2 ]
Whitehead, Amy [1 ,2 ]
Wilding, Sam [1 ,2 ]
Birtle, Alison J. [3 ,4 ]
Khoo, Vincent [5 ]
Jones, Robert J.
机构
[1] Univ Southampton, Southampton Clin Trials Unit, Southampton, Hants, England
[2] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England
[3] Univ Cent Lancashire, Lancashire Teaching Hosp NHS Fdn Trust, Preston, Lancs, England
[4] Univ Manchester, Preston, Lancs, England
[5] Royal Marsden NHS Fdn Trust, London, England
[6] Southampton Gen Hosp, Ctr Canc Immunol, Southampton Clin Trials Unit, Southampton SO16 6YD, Hants, England
关键词
AKT inhibitor; Capivasertib; Docetaxel; Metastatic castration-resistant; prostate cancer; PI3K; AKT; PTEN pathway; Phase; 2; trial; MITOXANTRONE; PREDNISONE;
D O I
10.1016/j.eururo.2022.05.019
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The PI3K/AKT/PTEN pathway is frequently deregulated in metastatic castration-resistant prostate cancer (mCRPC). ProCAID was a phase 2 trial assessing addition of the AKT1/2/3 inhibitor capivasertib to docetaxel for patients with mCRPC. We previously reported that capivasertib did not extend a composite progression-free survival primary endpoint but did significantly improve the secondary endpoint of overall survival (OS). Here we present OS data after 66% of events had occurred in the intent-to-treat population (n = 150). Median OS was 25.3 mo for capivasertib plus docetaxel versus 20.3 mo for placebo plus docetaxel (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.47-1.05; nominal p = 0.09). Receipt of subsequent life-extending treatments was balanced between the treatment arms. The OS benefit associated with capivasertib was maintained in a subset of patients previously treated with abiraterone and/or enzalutamide (median OS 25.0 vs 17.6 mo; HR 0.57, 95% CI 0.36-0.91; nominal p = 0.02) but not in abiraterone/enzalutamide-naive patients (median OS 31.1 mo vs not reached; HR 1.43, 95% CI 0.63-3.23). We conclude that OS may be extended by addition of capivasertib to docetaxel. Exploratory analysis revealed that the OS benefit was maintained in a subset of patients previously exposed to androgen recep-tor-targeted agents, which should be evaluated in prospective trials. Patient summary: The ProCAID study examined whether adding the AKT inhibitor drug capivasertib to docetaxel chemotherapy improves outcomes for patients with advanced prostate cancer. Initial analysis of the ProCAID results suggested that capivasertib improved overall survival benefit. This follow-up analysis suggests that capivasertib addi-tion may be particularly beneficial for patients whose cancer was previously treated with drugs that target the androgen receptor.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
引用
收藏
页码:512 / 515
页数:4
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