Pan-AKT inhibitor capivasertib with docetaxel and prednisolone in metastatic castration-resistant prostate cancer: a randomized, placebo-controlled phase II trial (ProCAID)
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, Tony
Westbury, C.
Sundar, S.
Robinson, A.
Jagdev, S.
Kumar, S.
Rooney, C.
Salinas-Souza, C.
Stephens, C.
Khoo, V.
Jones, R. J.
Affiliation
Southampton Clinical Trials Unit, University of Southampton, Southampton, United Kingdom.Issue Date
2020
Metadata
Show full item recordAbstract
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.Citation
Crabb SJ, Griffiths G, Marwood E, Dunkley D, Downs N, Martin K, et al. Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID). J Clin Oncol. 2021;39(3):190-201.Journal
Journal of Clinical OncologyDOI
10.1200/jco.20.01576PubMed ID
33326257Additional Links
https://dx.doi.org/10.1200/jco.20.01576Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1200/jco.20.01576
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