The PI3K/AKT/PTEN pathway is frequently deregulated in metastatic
castration-resistant
prostate cancer (mCRPC). ProCAID was a phase 2 trial assessing addition of the AKT1/2/3 inhibitor
capivasertib to
docetaxel for patients with mCRPC. We previously reported that
capivasertib did not extend a composite progression-free survival primary endpoint but did significantly improve the secondary endpoint of overall survival (OS). Here we present OS data after 66% of events had occurred in the intent-to-treat population (n = 150). Median OS was 25.3 mo for
capivasertib plus
docetaxel versus 20.3 mo for placebo plus
docetaxel (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.47-1.05; nominal p = 0.09). Receipt of subsequent life-extending treatments was balanced between the treatment arms. The OS benefit associated with
capivasertib was maintained in a subset of patients previously treated with
abiraterone and/or
enzalutamide (median OS 25.0 vs 17.6 mo; HR 0.57, 95% CI 0.36-0.91; nominal p = 0.02) but not in
abiraterone/
enzalutamide-naïve patients (median OS 31.1 mo vs not reached; HR 1.43, 95% CI 0.63-3.23). We conclude that OS may be extended by addition of
capivasertib to
docetaxel. Exploratory analysis revealed that the OS benefit was maintained in a subset of patients previously exposed to
androgen receptor-targeted agents, which should be evaluated in prospective trials. PATIENT SUMMARY: The ProCAID study examined whether adding the AKT inhibitor drug
capivasertib to
docetaxel chemotherapy improves outcomes for patients with advanced
prostate cancer. Initial analysis of the ProCAID results suggested that
capivasertib improved overall survival benefit. This follow-up analysis suggests that
capivasertib addition may be particularly beneficial for patients whose
cancer was previously treated with drugs that target the
androgen receptor.