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

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

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.

AKT inhibitor, Capivasertib, Docetaxel, Metastatic castration-resistant prostate cancer, PI3K/AKT/PTEN pathway, Phase 2 trial
0302-2838
512-515
Crabb, Simon J
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Griffiths, Gareth
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Dunkley, Denise
e98e58b2-c313-4aa4-8855-43887efe49b5
Downs, Nichola
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Ellis, Mary
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Radford, Mike
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Light, Michelle
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Northey, Josh
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Whitehead, Amy
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Wilding, Sam
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Birtle, Alison J
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Khoo, Vincent
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Jones, Robert J
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Crabb, Simon J
bcd1b566-7677-4f81-8429-3ab0e85f8373
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Dunkley, Denise
e98e58b2-c313-4aa4-8855-43887efe49b5
Downs, Nichola
f22ed202-1f46-4554-90b4-f40d3bf23393
Ellis, Mary
f9c39516-e078-4d80-807b-9ab91890df41
Radford, Mike
844eb99f-848e-4297-8c9a-6eaf992f3abf
Light, Michelle
6e2abe33-ca64-405e-9a4a-3e9739fb9a63
Northey, Josh
ab18c487-9933-4653-aa54-c2a118d7088f
Whitehead, Amy
7bd4e1d1-078b-4f2b-bfc9-ed44ba0a195a
Wilding, Sam
1f316b8b-db59-4289-b6aa-183f957f3470
Birtle, Alison J
5016770c-8e37-4c38-9215-3f745f24c6fe
Khoo, Vincent
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Jones, Robert J
ccc0201e-056c-4c4e-b4af-e35a0ee0860c

Crabb, Simon J, Griffiths, Gareth, Dunkley, Denise, Downs, Nichola, Ellis, Mary, Radford, Mike, Light, Michelle, Northey, Josh, Whitehead, Amy, Wilding, Sam, Birtle, Alison J, Khoo, Vincent and Jones, Robert J (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), 512-515. (doi:10.1016/j.eururo.2022.05.019).

Record type: Article

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.

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Accepted/In Press date: 2022
e-pub ahead of print date: 7 June 2022
Additional Information: Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
Keywords: AKT inhibitor, Capivasertib, Docetaxel, Metastatic castration-resistant prostate cancer, PI3K/AKT/PTEN pathway, Phase 2 trial

Identifiers

Local EPrints ID: 467985
URI: http://eprints.soton.ac.uk/id/eprint/467985
ISSN: 0302-2838
PURE UUID: bdbdd69d-7163-4373-b7aa-a72f01b3ea61
ORCID for Simon J Crabb: ORCID iD orcid.org/0000-0003-3521-9064
ORCID for Gareth Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

Catalogue record

Date deposited: 27 Jul 2022 16:51
Last modified: 17 Nov 2022 02:42

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Contributors

Author: Simon J Crabb ORCID iD
Author: Denise Dunkley
Author: Nichola Downs
Author: Mary Ellis
Author: Mike Radford
Author: Michelle Light
Author: Josh Northey
Author: Amy Whitehead
Author: Sam Wilding
Author: Alison J Birtle
Author: Vincent Khoo
Author: Robert J Jones

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