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Lookup NU author(s): Dr Pasquale RescignoORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 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.
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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