Pan-AKT inhibitor capivasertib with docetaxel and prednisolone in metastatic castration-resistant prostate cancer: a randomized, placebo-controlled phase II trial (ProCAID)

Crabb, S. J. et al. (2021) Pan-AKT inhibitor capivasertib with docetaxel and prednisolone in metastatic castration-resistant prostate cancer: a randomized, placebo-controlled phase II trial (ProCAID). Journal of Clinical Oncology, 39(3), pp. 190-201. (doi: 10.1200/JCO.20.01576) (PMID:33326257)

Abstract

Purpose: Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel. Patients and Methods: ProCAID was a placebo controlled randomized phase II trial in mCRPC. Patients received up to ten 21-day cycles of docetaxel (75 mg/m2 intravenous, day 1) and prednisolone (5 mg twice daily, oral, day 1-21) and were randomly assigned (1:1) to oral capivasertib (320 mg twice daily, 4 days on/3 days off, from day 2 each cycle), or placebo, until disease progression. Treatment allocation used minimization factors: bone metastases; visceral metastases; investigational site; and prior abiraterone or enzalutamide. The primary objective, by intention to treat, determined if the addition of capivasertib prolonged a composite progression-free survival (cPFS) end point that included prostate-specific antigen progression events. cPFS and overall survival (OS) were also assessed by composite biomarker subgroup for PI3K/AKT/PTEN pathway activation status. Results: One hundred and fifty patients were enrolled. Median cPFS was 7.03 (95% CI, 6.28 to 8.25) and 6.70 months (95% CI, 5.52 to 7.36) with capivasertib and placebo respectively (hazard ratio [HR], 0.92; 80% CI, 0.73 to 1.16; one-sided P = .32). Median OS was 31.15 (95% CI, 20.07 to not reached) and 20.27 months (95% CI, 17.51 to 24.18), respectively (HR, 0.54; 95% CI, 0.34 to 0.88; two-sided P = .01). cPFS and OS results were consistent irrespective of PI3K/AKT/PTEN pathway activation status. Grade III-IV adverse events were equivalent between arms (62.2%). The most common adverse events of any grade deemed related to capivasertib were diarrhea, fatigue, nausea, and rash. Conclusion: The addition of capivasertib to chemotherapy did not extend cPFS in mCRPC irrespective of PI3K/AKT/PTEN pathway activation status. The observed OS result (a secondary end point) will require prospective validation in future studies to address potential for bias.

• Item Type: Articles
• Additional Information: ProCAID was investigator initiated and funded by Cancer Research UK (C9317/A16029, CRUK/12/042).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jones, Professor Robert
• Authors: Crabb, S. J., Griffiths, G., Marwood, E., Dunkley, D., Downs, N., Martin, K., Light, M., Northey, J., Wilding, S., Whitehead, A., Shaw, E., Birtle, A. J., Bahl, A., Elliott, T., Westbury, C., Sundar, S., Robinson, A., Jagdev, S., Kumar, S., Rooney, C., Salinas-Souza, C., Stephens, C., Khoo, V., and Jones, R. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Clinical Oncology
• Publisher: American Society of Clinical Oncology
• ISSN: 0732-183X
• ISSN (Online): 1527-7755
• Published Online: 16 December 2020
• Copyright Holders: Copyright © 2020 American Society of Clinical Oncology
• First Published: First published in Journal of Clinical Oncology 39(3):190-201
• Publisher Policy: Reproduced under a Creative Commons License