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Advances in mCRPC

CE / CME

Advances in Metastatic Castration-Resistant Prostate Cancer: Biomarker-Driven Treatment Strategies and Emerging Therapeutic Approaches

ABIM MOC: maximum of 0.50 Medical Knowledge MOC point

Physicians: Maximum of 0.50 AMA PRA Category 1 Credit™

Released: July 20, 2026

Expiration: January 19, 2027

Neal D. Shore
Neal D. Shore, MD, FACS
CME/CE Information

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Capivasertib: Mechanism of Action

Capivasertib is an orally available pan-AKT kinase inhibitor that targets the PI3K/AKT pathway. PTEN deficiency, which may be identified by IHC and can also be associated with gene alterations, can lead to overactivation of this pathway. By targeting this pathway, capivasertib is intended to address this biologic mechanism and may ultimately contribute to apoptotic effects. It can also be used in combination with ARPIs. In this setting, capivasertib is being evaluated in combination with abiraterone acetate and prednisone/prednisolone.3

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ProCAID Trial of Docetaxel ± Capivasertib in mCRPC:​ OS Results in ITT Population

The phase I/II ProCAID trial examined docetaxel with or without capivasertib. This was a proof-of-concept study aimed to determine whether capivasertib addition could improve outcomes for patients with mCRPC. The primary endpoint was PFS, and OS was a secondary endpoint.

In the intention-to-treat population, median OS was numerically longer with capivasertib plus docetaxel than with placebo plus docetaxel (25.3 vs 20.3 months), with an HR of 0.70 and P = .09.21 

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ProCAID Trial of Docetaxel ± Capivasertib in mCRPC:​ OS With or Without Prior ARPI Exposure

In exploratory analyses by prior AR-targeted agent exposure, the apparent OS effect of capivasertib plus docetaxel appeared more favorable in patients who had previously received abiraterone and/or enzalutamide than in those without prior exposure.21 These findings helped support continued investigation of AKT pathway inhibition in prostate cancer.

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CAPItello-281: Abiraterone ± Capivasertib in PTEN-Deficient mHSPC

The phase III CAPItello-281 trial randomized approximately 1000 patients to abiraterone with or without capivasertib. Patients were required to have de novo mHSPC and loss of PTEN, a highly selective biomarker. The primary endpoint was rPFS. 

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CAPItello-281: Radiographic progression-free survival

CAPItello-281 met its primary endpoint. Median rPFS was 33.2 months for the capivasertib plus abiraterone group and 25.7 months for the placebo plus abiraterone group, with an HR of 0.81 (P = .034). The OS data were immature at this interim analysis.22 

These findings support AKT pathway inhibition as a clinically relevant strategy for patients with PTEN-deficient metastatic APM-naive/sensitive prostate cancer.

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CAPItello-281: Most Common TEAEs

The most common treatment-emergent adverse events (TEAEs) of any grade in the capivasertib plus abiraterone group were diarrhea, hyperglycemia, and rash, with some grade 3 or higher events. Overall, the safety profile was consistent with the known profiles of each individual agent.22 Most are manageable and typically not uncommon to medical oncologists. I think that for a patient who is PTEN deficient, this combination strategy should be included in shared decision-making. The findings of this trial were the basis for the recent approval of capivasertib in combination with abiraterone and prednisone for adults with PTEN-deficient mAPMN/S prostate cancer, or mHSPC.3 In appropriate patients, this regimen should be discussed through shared decision-making, with attention to glucose monitoring, rash, diarrhea, and supportive care.

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