In de novo mHSPC (also known as metastatic androgen pathway modulation-naïve/sensitive prostate cancer), PTEN deficiency is associated with poor prognosis despite current standard of care. CAPItello-281 (NCT04493853) met its primary endpoint showing a statistically significant radiographic progression-free survival (rPFS) benefit with capi + abi vs pbo + abi in PTEN-deficient de novo mHSPC (maturity: 39.3% rPFS; 26.4% OS). To provide more mature data, a descriptive analysis of efficacy, including OS (41.6% maturity), and safety for CAPItello-281 was conducted.
Pts with de novo mHSPC and PTEN-deficient tumours (defined as ≥90% of viable malignant cells with no specific cytoplasmic staining by immunohistochemistry [IHC]) received capi or pbo (1:1) + abi, pred and androgen deprivation therapy. OS was a descriptive alpha-controlled key secondary endpoint; rPFS was descriptive. Efficacy in post hoc exploratory PTEN deficiency (by IHC) subgroups and safety were also assessed.
1012 pts received capi + abi (N=507) or pbo + abi (N=505). At this ad hoc data cutoff (DCO; 9 March 2026), the HR for OS was improved from the primary DCO and favoured capi + abi vs pbo + abi (41.6% maturity; HR 0.82 [95% CI 0.68, 0.99]; median OS 57.4 vs 46.5 mo; table). rPFS favoured capi + abi (52.6% maturity; 0.83 [0.70, 0.99]; 35.5 vs 26.0 mo). OS HRs at increasing PTEN-deficiency cutoffs (≥95%, n=814 to 100%, n=331) ranged from 0.76–0.74. With 17 mo additional follow-up, the capi + abi safety profile was consistent with the primary DCO. Table: LBA56
| Overall population | Ad hoc DCO (9 Mar 2026) | Primary DCO (7 Oct 2024) | ||
| Capi + abi (N=507) | Pbo + abi (N=505) | Capi + abi (N=507) | Pbo + abi (N=505) | |
| OS | ||||
| E, n (%) | 421 (41.6) | 267 (26.4) | ||
| Median, mo (95% CI) | 57.4 (47.0, NC) | 46.5 (40.7, 53.2) | NC (42.5, NC) | NC (NC, NC) |
| HR (95% CI) | 0.82 (0.68, 0.99) | 0.90 (0.71, 1.15) | ||
| P | 0.044* | 0.401 | ||
| rPFS | ||||
| E, n (%) | 532 (52.6) | 398 (39.3) | ||
| Median, mo (95% CI) | 35.5 (29.7, 40.5) | 26.0 (22.4, 31.3) | 33.2 (25.8, 44.2) | 25.7 (22.0, 29.9) |
| HR (95% CI) | 0.83 (0.70, 0.99) | 0.81 (0.66, 0.98) | ||
| P | 0.033 (nominal)† | 0.034 | ||
*Descriptive OS analysis: alpha controlled, did not meet statistical significance; †Descriptive rPFS analysis, not formally tested. CI, confidence interval; E, events; HR, hazard ratio, NC, not calculable.
This descriptive analysis demonstrates an improved HR for OS vs the primary DCO and consistent rPFS benefit with capi + abi vs pbo + abi, addressing the poor outcomes and unmet need in PTEN-deficient de novo mHSPC. The safety profile of capi + abi remains consistent with primary DCO. Capi + abi represents a first-in-class targeted treatment for this population.
NCT04493853.
Medical writing assistance was provided by Tobias M Hedison, PhD, and Andrew Briggs, MA, of Amiculum Business Services Ltd, funded by AstraZeneca.
AstraZeneca.