Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study
Rattachement africain : fr, gb, de, jp, br, tr, pl, es, cn, au, kr, nl, th, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND: In metastatic hormone-sensitive prostate cancer (mHSPC), phosphatase and tensin homolog (PTEN) deficiency results in phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway activation, providing an independent proliferative drive, which cannot be suppressed by androgen receptor pathway inhibitors (ARPIs), resulting in worse outcomes. Dual inhibition of PI3K/AKT and AR pathways with capivasertib and abiraterone may delay progression and improve disease outcomes. PATIENTS AND METHODS: In CAPItello-281 (NCT04493853), patients with PTEN-deficient mHSPC (diagnostic cut-off: ≥90% viable malignant cells with no specific cytoplasmic PTEN immunohistochemistry staining) received capivasertib or placebo (1 : 1) plus abiraterone, prednisone/prednisolone, and androgen deprivation therapy (ADT). The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS); overall survival (OS) was a key secondary endpoint. Post hoc exploratory subgroups at increasing PTEN cut-off thresholds were also assessed. RESULTS: 25.3% (1519/6003) of patients with valid tumor test results had PTEN-deficient tumors. In the randomized PTEN-deficient population, a statistically significant improvement in rPFS was observed with capivasertib plus abiraterone (n = 507, median 33.2 months) versus placebo plus abiraterone [n = 505, 25.7 months; hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.66-0.98, P = 0.034]. Post hoc rPFS analyses for loss of PTEN cut-offs of ≥95%, ≥99%, and 100% showed that the capivasertib plus abiraterone arm performed consistently across cut-offs, but the placebo plus abiraterone arm performed progressively worse as the cut-off for the degree of PTEN loss was increased, resulting in a numerically improved treatment effect. In the overall population studied, the HR for OS (26.4% maturity) was 0.90, 95% CI 0.71-1.15, P = 0.401. The most common adverse events (AEs) for capivasertib plus abiraterone were diarrhea (51.9%; 8.0% placebo plus abiraterone), hyperglycemia (38.0%; 12.9%), and rash (35.4%; 7.0%). Deaths associated with an AE were reported in 36 (7.2%) and 26 (5.2%) patients in the capivasertib plus abiraterone and placebo plus abiraterone arms, respectively. CONCLUSIONS: Capivasertib plus abiraterone improves rPFS versus placebo plus abiraterone in PTEN-deficient mHSPC, on a background of ADT, with a 7.5-month improvement in median rPFS. AE profile was consistent with that of the individual agents. Patients with PTEN-deficient mHSPC benefit from dual blockade of the PI3K/AKT and AR pathways with capivasertib plus abiraterone.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study
- Date Crossref
- 01/01/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Institut Gustave Roussy pays non établi dans la noticeStructure de recherche
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Centre Oscar Lambret pays non établi dans la noticeÉtablissement de santé
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Salford Royal NHS Foundation Trust pays non établi dans la noticeÉtablissement de santé
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Charité - Universitätsmedizin Berlin pays non établi dans la noticeÉtablissement de santé
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Instituto de Investigación Sanitaria del Principado de Asturias pays non établi dans la noticeStructure de recherche
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Institut Gustave Roussy, Centre Oscar Lambret et Salford Royal NHS Foundation Trust, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.