Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial.
Date
2024-07-01ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
AKT-inhibitor
Enzalutamide
PTEN
Phase II randomized trial
Prostate cancer
Humans
Male
Prostatic Neoplasms, Castration-Resistant
Phenylthiohydantoin
Benzamides
Docetaxel
Aged
Antineoplastic Combined Chemotherapy Protocols
Middle Aged
Nitriles
Double-Blind Method
Pyrimidines
Androstenes
Aged, 80 and over
Pyrroles
Research team
Clin Trials & Stats Unit
Cancer Biomarkers
PrCa Targeted Therapy
Language
eng
Date accepted
2024-04-28
License start date
2024-07-01
Citation
European Journal of Cancer, 2024, 205 pp. 114103 -
Publisher
ELSEVIER SCI LTD