Capivasertib plus abiraterone in PTEN-deficient de novo metastatic hormone-sensitive prostate cancer: updated survival analysis from CAPItello-281

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.