Overall survival update for patients with metastatic castration-resistant prostate cancer treated with capivasertib and docetaxel in the phase 2 ProCAID clinical trial

Crabb, S. J. et al. (2022) Overall survival update for patients with metastatic castration-resistant prostate cancer treated with capivasertib and docetaxel in the phase 2 ProCAID clinical trial. European Urology, 82(5), pp. 512-515. (doi: 10.1016/j.eururo.2022.05.019) (PMID:35688662)

Abstract

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-naïve 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 receptor–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 addition may be particularly beneficial for patients whose cancer was previously treated with drugs that target the androgen receptor.

• Item Type: Articles
• Additional Information: Funding was provided by Cancer Research UK (C9317/A16029, CRUK/12/042) and AstraZeneca. The study was also supported by core funding from the Southampton Clinical Trial Unit.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jones, Professor Robert
• Authors: Crabb, S. J., Griffiths, G., Dunkley, D., Downs, N., Ellis, M., Radford, M., Light, M., Northey, J., Whitehead, A., Wilding, S., Birtle, A. J., Khoo, V., and Jones, R. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: European Urology
• Publisher: Elsevier
• ISSN: 0302-2838
• ISSN (Online): 1873-7560
• Published Online: 07 June 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in European Urology 82(5): 512-515
• Publisher Policy: Reproduced under a Creative Commons License