FDA Approves Capivasertib Plus Abiraterone and Prednisone for Prostate Cancer

The FDA has approved capivasertib (Truqap; AstraZeneca) in combination with abiraterone (Zytiga; Janssen Pharmaceuticals) and prednisone as treatment for adults with PTEN-deficient metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer. This approval represents the first indication for capivasertib in this patient population and introduces a biomarker-driven treatment option for patients whose tumors exhibit PTEN deficiency.¹

Along with the approval, the FDA further authorized the VENTANA PTEN (SP218) RxDx assay (Ventana Medical Systems, Roche Diagnostics) as a companion diagnostic to identify patients eligible for treatment with capivasertib.¹ This decision progressively emphasizes the developing role of precision oncology in prostate cancer management, where molecular profiling is increasingly informing treatment selection.

One of the most commonly diagnosed malignancies among men worldwide remains prostate cancer. While androgen deprivation therapy and androgen receptor pathway inhibitors have significantly improved outcomes for patients with metastatic hormone-sensitive disease, resistance eventually develops in many patients.² PTEN loss is among the most frequently altered tumor suppressor pathways in advanced prostate cancer and is associated with activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, which promotes tumor growth and treatment resistance.³

Capivasertib is an oral inhibitor of all 3 AKT isoforms (AKT1, AKT2, and AKT3). Through inhibiting AKT signaling, capivasertib targets a critical pathway activated in tumors with PTEN loss, providing a biologically rational strategy for improving outcomes in this high-risk patient population.³ Prior data has demonstrated activity of AKT inhibition across several solid tumors characterized by aberrant PI3K/AKT pathway signaling.⁴

The approval is supported by findings from the phase 3 CAPItello-281 trial (NCT04305496), a randomized, double-blind, placebo-controlled, multicenter trial that enrolled 1012 adults with newly diagnosed PTEN-deficient mAPMN/S prostate cancer. PTEN deficiency was prospectively determined using the immunohistochemistry-based VENTANA PTEN (SP218) RxDx assay and was defined as the absence of specific cytoplasmic staining in at least 90% of viable malignant cells.¹

The participants of the trial were randomly assigned to receive capivasertib plus abiraterone or placebo plus abiraterone. Abiraterone was administered in combination with either prednisone or prednisolone. The primary end point was radiographic progression-free survival (rPFS), based on data assessments, with overall survival serving as an additional efficacy end point.¹

Results from the data displayed a statistically significant improvement in rPFS among patients treated with capivasertib and abiraterone compared with placebo and abiraterone. Median rPFS was 33.2 months (95% CI, 25.8-44.2) in the capivasertib arm versus 25.7 months (95% CI, 22.0-29.9) in the placebo arm, corresponding to an approximate 19% reduction in the risk of radiographic progression or death (HR, 0.81 [95% CI, 0.66-0.98]; P = .034).¹ Overall survival data were immature at the time of the analysis.¹

The prescribing information for capivasertib includes warnings and precautions in regards to hyperglycemia, diarrhea, cutaneous adverse reactions, and embryo-fetal toxicity. The recommended dose is 400 mg orally twice daily, administered on a schedule of 4 days on treatment followed by 3 days off. Treatment is continued until disease progression or unacceptable toxicity. It is recommended that patients receive concurrent gonadotropin-releasing hormone analog therapy unless they have undergone bilateral orchiectomy.¹

REFERENCES

1. FDA. FDA approves capivasertib with abiraterone and prednisone for PTEN-deficient androgen pathway modulation-naïve or -sensitive prostate cancer. June 12, 2026. Accessed June 15, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-abiraterone-and-prednisone-pten-deficient-androgen-pathway-modulation

2. National Cancer Institute. Prostate Cancer Treatment (PDQ®)–Health Professional Version. Updated 2025. Accessed June 15, 2026. https://www.cancer.gov/types/prostate/hp/prostate-treatment-pdq

3. Smyth LM, Tamura K, Oliveira M, et al. Capivasertib, an AKT kinase inhibitor, as monotherapy or in combination with fulvestrant in patients with AKT1E17K-mutant, ER-positive metastatic breast cancer. Clin Cancer Res. 2020;26(15):3947-3957. doi:10.1158/1078-0432.CCR-19-3953

4. de Bono JS, De Giorgi U, Rodrigues DN, et al. Randomized phase II study evaluating AKT blockade with ipatasertib, in combination with abiraterone, in patients with metastatic prostate cancer with and without PTEN loss. Clin Cancer Res. 2019;25(3):928-936. doi:10.1158/1078-0432.CCR-18-0981