期刊
EUROPEAN UROLOGY
卷 82, 期 5, 页码 512-515出版社
ELSEVIER
DOI: 10.1016/j.eururo.2022.05.019
关键词
AKT inhibitor; Capivasertib; Docetaxel; Metastatic castration-resistant; prostate cancer; PI3K; AKT; PTEN pathway; Phase 2 trial
资金
- Cancer Research UK [C9317/A16029, CRUK/12/042]
- AstraZeneca
- Southampton Clinical Trial Unit
The addition of capivasertib to docetaxel may extend overall survival in patients with metastatic castration-resistant prostate cancer. Subgroup analysis suggests that the benefit is maintained in patients previously treated with androgen receptor-targeted agents.
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/).
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