Capivasertib plus abiraterone in PTEN-deficient de novo metastatic hormone-sensitive prostate cancer: updated survival analysis from CAPItello-281
In brief
Capivasertib plus abiraterone reached 57-month median survival in PTEN-deficient prostate cancer
In 1,012 men with newly diagnosed metastatic, hormone-sensitive prostate cancer and PTEN-deficient tumors, median overall survival was 57.4 months with capivasertib plus abiraterone, versus 46.5 months with abiraterone alone. The analysis was ad hoc and descriptive, with only 42% of overall-survival data mature, so longer follow-up is needed to clarify the benefit.
- Journal
- Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
- Published
- 23 October 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- K Fizazi, N W Clarke, M De Santis, H Uemura, A P Fay, N Karadurmus, et al.
- PMID
- 42918424
- DOI
- 10.1016/j.annonc.2026.10.097
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 25 October 2026): Updated targeted-therapy survival analysis in PTEN-deficient prostate cancer
Abstract
BACKGROUND: Patients with phosphatase and tensin homolog (PTEN)-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC) have poor prognosis and reduced benefit from current standard of care. The phase III CAPItello-281 study (NCT04493853) showed a statistically significant benefit in radiographic progression-free survival (rPFS) with capivasertib plus abiraterone versus placebo plus abiraterone (combined with prednisone/prednisolone and androgen deprivation therapy): hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.66-0.98; P=0.034. The HR for interim overall survival (OS; 26% maturity) was 0.90, 95% CI 0.71-1.15. Here, we report ad hoc, descriptive analyses at 42% OS data maturity. PATIENTS AND METHODS: Patients with de novo mHSPC and PTEN-deficient tumors (defined as ≥90% of viable malignant cells with no specific cytoplasmic staining by immunohistochemistry) received capivasertib plus abiraterone or matched placebo (randomized 1:1) plus abiraterone. Analyses performed at this ad hoc data cut-off, including the alpha-controlled key secondary endpoint of OS as well as the primary endpoint of investigator-assessed rPFS, were descriptive and not prespecified in the protocol. RESULTS: 1012 patients received capivasertib plus abiraterone (n=507) or placebo plus abiraterone (n=505). At this ad hoc analysis at 42% OS maturity (data cut-off: March 9, 2026), with 17 months' additional follow-up (median follow-up 39 months in both arms), HR for OS favored capivasertib plus abiraterone versus placebo plus abiraterone (HR 0.82, 95% CI 0.68-0.99, P=0.044) and OS medians were reached: 57.4 versus 46.5 months. Updated rPFS (HR 0.83, 95% CI 0.70-0.99, nominal P=0.033; median 35.5 versus 26.0 months) was consistent with the primary analysis. The safety profile remained consistent with the primary findings. CONCLUSIONS: With longer follow-up, findings from this updated descriptive analysis support the clinically meaningful OS benefit of adding capivasertib to abiraterone in the treatment of patients with PTEN-deficient mHSPC. Capivasertib plus abiraterone represents a first-in-class targeted treatment approach for this poor prognosis population with high unmet need.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.