Rescigno, Pasquale;
Porta, Nuria;
Finneran, Laura;
Riisnaes, Ruth;
Figueiredo, Ines;
Carreira, Suzanne;
Flohr, Penny;
... De Bono, Johann; + view all
(2024)
Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial.
European Journal of Cancer
, 205
, Article 114103. 10.1016/j.ejca.2024.114103.
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Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abirat.pdf - Published Version Download (2MB) | Preview |
Abstract
Background: 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.
| Type: | Article |
|---|---|
| Title: | Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejca.2024.114103 |
| Publisher version: | https://doi.org/10.1016/j.ejca.2024.114103 |
| Language: | English |
| Additional information: | Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/bync/4.0/). |
| Keywords: | Enzalutamide; AKT-inhibitor; PTEN; Prostate cancer; Phase II randomized trial |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217443 |
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