Capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in patients (pts) with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC): Updated overall survival (OS) from CAPItello-281

doi:10.1016/j.annonc.2026.10.097

CAPItello-281

Paciente / Población Intervención / Exposición Comparación Desenlace

In patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer, capivasertib plus abiraterone did not significantly improve overall survival compared with placebo plus abiraterone at this updated analysis, although the hazard ratio favoured capivasertib.

N

1012pacientes

Diseño

Randomised 1:1, placebo-controlled trial in patients with de novo metastatic hormone-sensitive prostate cancer and PTEN-deficient tumours by immunohistochemistry, comparing capivasertib plus abiraterone with placebo plus abiraterone, both with prednisone and androgen deprivation therapy (NCT04493853).

Desenlace

Radiographic progression-free survival (rPFS), met at the primary analysis. Overall survival was the alpha-controlled key secondary endpoint.

ResultadoAt the ad hoc data cutoff (9 March 2026), rPFS with capivasertib plus abiraterone 35.5 vs 26.0 months with placebo plus abiraterone (52.6% maturity; HR 0.83, 95% CI 0.70-0.99; nominal P = 0.033, not formally tested). At the primary data cutoff (7 October 2024), rPFS was 33.2 vs 25.7 months (HR 0.81, 95% CI 0.66-0.98; P = 0.034). Median overall survival 57.4 vs 46.5 months (41.6% maturity; HR 0.82, 95% CI 0.68-0.99; P = 0.044), an alpha-controlled analysis that did not meet statistical significance. At the primary data cutoff, the overall survival HR was 0.90 (95% CI 0.71-1.15; P = 0.401). In post hoc subgroups with PTEN deficiency of 95% (n=814) up to 100% (n=331), overall survival HRs ranged from 0.76 to 0.74. With 17 months of additional follow-up, the safety profile was consistent with the primary data cutoff.

Fizazi K, Clarke N, De Santis M, et al. Annals of Oncology. 2026. 10.1016/j.annonc.2026.10.097

Discusión y crítica

This ad hoc descriptive update shows a hazard ratio for overall survival that favours capivasertib and has moved from 0.90 to 0.82 with more follow-up. However, the alpha-controlled overall survival analysis did not meet statistical significance, and at 41.6% maturity the median for the capivasertib arm still has a non-calculable upper confidence limit. The rPFS benefit at this cutoff is nominal only, and the stronger hazard ratios at stricter PTEN-deficiency cutoffs come from post hoc exploratory subgroups, so they generate hypotheses rather than confirm them. The abstract gives no adverse event rates, discontinuations, blinding details, trial phase or subsequent therapies, so neither tolerability nor what drove the survival result can be judged from it.