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Ref Type Journal Article
PMID (41120017)
Authors Fizazi K, Clarke NW, De Santis M, Uemura H, Fay AP, Karadurmus N, Kwiatkowski M, Alvarez-Fernandez C, Jiang S, Sotelo M, Parslow D, Oliveira N, Kwon TG, Ye D, Boudewijns S, Danchaivijitr P, Rooney C, Gresty C, Yeste-Velasco M, Logan J, George DJ, CAPItello-281 Study Group
Title Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study.
Journal Vol Issue Date Pages Journal Short Title
Annals of oncology : official journal of the European Society for Medical Oncology 37 1 2026 Jan 53-68 Ann Oncol
URL
Abstract Text 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.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.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.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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PTEN negative prostate cancer sensitive Abiraterone + Capivasertib + Prednisone FDA approved - On Companion Diagnostic Actionable In a Phase III trial (CAPItello-281) that supported FDA approval, addition of Truqap (capivasertib) to Zytiga (abiraterone), Adasone (prednisone), and androgen deprivation therapy significantly improved radiographic progression-free survival (33.2 vs 25.7 mo, HR 0.81, p=0.034) compared to placebo in patients with PTEN-deficient (>/=90% tumor cells with no cytoplasmic PTEN by IHC) metastatic hormone-sensitive prostate cancer (PMID: 41120017; NCT04493853). detail... 41120017 detail...