Overall Survival Update for Patients with Metastatic Castration-resistant Prostate Cancer Treated with Capivasertib and Docetaxel in the Phase 2 ProCAID Clinical Trial

• Published in: European urology 2022-11, Vol.82 (5), p.512-515
• Main Authors: Crabb, Simon J., Griffiths, Gareth, Dunkley, Denise, Downs, Nichola, Ellis, Mary, Radford, Mike, Light, Michelle, Northey, Josh, Whitehead, Amy, Wilding, Sam, Birtle, Alison J., Khoo, Vincent, Jones, Robert J.
• Format: Article
• Language: English
• Subjects: AKT inhibitor; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Benzamides; Capivasertib; Disease-Free Survival; Docetaxel; Docetaxel - therapeutic use; Humans; Male; Metastatic castration-resistant prostate cancer; Nitriles - therapeutic use; Phase 2 trial; Phenylthiohydantoin; Phosphatidylinositol 3-Kinases; PI3K/AKT/PTEN pathway; Prospective Studies; Prostatic Neoplasms, Castration-Resistant - pathology; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyrroles; Receptors, Androgen; Treatment Outcome
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2022.05.019

ProCAID tested the benefit of using the AKT inhibitor capivasertib with chemotherapy to treat advanced castration-resistant prostate cancer. This updated analysis provides evidence that capivasertib addition extends overall survival in patients who have previously received abiraterone and/or enzalutamide. 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. 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.