# CAPItello-281

Source: https://onco.cc/trials/capitello-281/  
OnCo record `capitello-281` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

CAPItello-281 delivered the first AKT inhibitor success in prostate cancer, for the ~25% of men whose tumours have lost PTEN on the trial's own immunohistochemistry cut-off.

## Summary

CAPItello-281, trial NCT04493853 sponsored by AstraZeneca and reported in 2025, delivered the first AKT inhibitor success in prostate cancer, for the roughly quarter of men whose tumours have lost PTEN on its own immunohistochemistry cut-off, 1,519 of 6,003 tested. It randomised 1,012 men with de novo metastatic hormone-sensitive, PTEN-deficient prostate cancer to abiraterone with capivasertib or placebo, met its primary radiographic progression-free survival endpoint with topline results in November 2024 presented in 2025, and led to FDA approval in the second quarter of 2026, with diarrhoea, rash and raised blood sugar as the class effects. OnCo links it to AKT as a target, to the PI3K, AKT and mTOR pathway, and to capivasertib and abiraterone acetate. It is a single pivotal trial with immature overall survival, and whether the modest progression benefit justifies the added toxicity is the open question. Capivasertib has its own page.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Registry id: NCT04493853
- Phase: 3
- Setting: De novo metastatic hormone-sensitive prostate cancer with PTEN deficiency: abiraterone + capivasertib vs abiraterone + placebo
- Sponsor: AstraZeneca
- Enrolled: 1012
- Result: Median rPFS 33.2 against 25.7 months, HR 0.81 (95% CI 0.66 to 0.98, p=0.034); OS HR 0.90 at 26.4% maturity; approved 2026.
- Outcomes: Radiographic progression-free survival, PTEN-deficient mHSPC: Capivasertib + abiraterone + ADT 40 months vs Placebo + abiraterone + ADT 31.7 months, HR 0.81
- Replication: Single pivotal trial; OS immature.

## Sources

- ClinicalTrials.gov NCT04493853: https://clinicaltrials.gov/study/NCT04493853

## Connected records

- cancers: [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [PI3K, AKT and mTOR inhibitors](https://onco.cc/technologies/pi3k-akt-mtor-inhibitors/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [AKT](https://onco.cc/targets/akt/)
- drugs: [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Capivasertib](https://onco.cc/drugs/capivasertib/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- pathways: [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- key papers: [Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study](https://onco.cc/key-papers/paper-capitello-281-ann-oncol-2026/)
- ideas: [Prescribe a quarter dose of abiraterone with breakfast](https://onco.cc/ideas/idea-cost-low-dose-abiraterone-food/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)

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