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

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.

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

All Authors

Rescigno, P.

Porta, N.

Finneran, L.

Riisnaes, R.

Figueiredo, I.

Carreira, S.

Flohr, P.

Miranda, S.

Bertan, C.

Ferreira, A.

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LTHT Author

Ralph, Christy

LTHT Department

Leeds Cancer Centre
Oncology

Publication Date

2024

Item Type

Journal Article
Clinical Trial, Phase II
Randomized Controlled Trial
Multicenter Study

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.