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Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial

Lookup NU author(s): Dr Pasquale RescignoORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

© 2024 The AuthorsBackground: PTEN loss and aberrations in PI3K/AKT signaling kinases associate with poorer response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC). In this study, we assessed antitumor activity of the AKT inhibitor capivasertib combined with enzalutamide in mCRPC with prior progression on AA and docetaxel. Methods: This double-blind, placebo-controlled, randomized phase 2 trial, recruited men ≥ 18 years with progressing mCRPC and performance status 0–2 from 15 UK centers. Randomized participants (1:1) received enzalutamide (160 mg orally, once daily) with capivasertib (400 mg)/ placebo orally, twice daily on an intermittent (4 days on, 3 days off) schedule. Primary endpoint was composite response rate (RR): RECIST 1.1 objective response, ≥ 50 % PSA decrease from baseline, or circulating tumor cell count conversion (from ≥ 5 at baseline to < 5 cells/7.5 mL). Subgroup analyses by PTENIHC status were pre-planned. Results: Overall, 100 participants were randomized (50:50); 95 were evaluable for primary endpoint (47:48); median follow-up was 43 months. RR were 9/47 (19.1 %) enzalutamide/capivasertib and 9/48 (18.8 %) enzalutamide/placebo (absolute difference 0.4 % 90 %CI −12.8 to 13.6, p = 0.58), with similar results in the PTENIHC loss subgroup. Irrespective of treatment, OS was significantly worse for PTENIHC loss (10.1 months [95 %CI: 4.6–13.9] vs 14.8 months [95 %CI: 10.8–18]; p = 0.02). Most common treatment-emergent grade ≥ 3 adverse events for the combination were diarrhea (13 % vs 2 %) and fatigue (10 % vs 6 %). Conclusions: Combined capivasertib/enzalutamide was well tolerated but didn't significantly improve outcomes from abiraterone pre-treated mCRPC.


Publication metadata

Author(s): Rescigno P, Porta N, Finneran L, Riisnaes R, Figueiredo I, Carreira S, Flohr P, Miranda S, Bertan C, Ferreira A, Crespo M, Rodrigues DN, Gurel B, Nobes J, Crabb S, Malik Z, Ralph C, McGovern U, Hoskin P, Jones RJ, Birtle A, Gale J, Sankey P, Jain S, McLaren D, Chadwick E, Espinasse A, Hall E, de Bono J

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer

Year: 2024

Volume: 205

Print publication date: 01/07/2024

Online publication date: 08/05/2024

Acceptance date: 28/04/2024

Date deposited: 21/05/2024

ISSN (print): 0959-8049

ISSN (electronic): 1879-0852

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.ejca.2024.114103

DOI: 10.1016/j.ejca.2024.114103

Data Access Statement: The ICR-CTSU supports the wider dissemination of information from its research and increased cooperation between investigators. Trial data are collected, managed, stored, shared, and archived according to ICR-CTSU Standard Operating Procedures to ensure the enduring quality, integrity, and utility of the data. Formal requests for data sharing are considered in line with ICR-CTSU procedures with due regard given to funder and sponsor guidelines. [Further details at https://www.sciencedirect.com/science/article/pii/S0959804924007597?via%3Dihub#sec0080 ]


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Funding

Funder referenceFunder name
C1491/A25351
Cancer Research UK
CTUQQR-Dec22/100004
Institute of Cancer Research
National Institute of Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust
Prostate Cancer Foundation Young Investigator Awards

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