FDA approves capivasertib plus abiraterone and prednisone for PTEN-deficient mHSPC

On June 12, 2026, the FDA approved capivasertib (Truqap) in combination with abiraterone (Zytiga) and prednisone for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer [previously metastatic hormone-sensitive prostate cancer (mHSPC)], as detected by an FDA-authorized test.¹

The agency also concurrently approved a companion diagnostic test to detect PTEN deficiency in tumors of patients with prostate adenocarcinoma.

“Patients with PTEN-deficient metastatic hormone-sensitive prostate cancer, now called metastatic androgen pathway modulation-naïve or sensitive prostate cancer, experience faster progression and worse prognosis than those without PTEN deficiency,” explained Daniel J. George, MD, Director of Genitourinary Oncology at Duke Cancer Institute, in a news release.1 “Keeping patients with this form of prostate cancer in remission and free from disease progression as long as possible is a high priority.” Today’s landmark approval of the capivasertib combination as the first and only targeted treatment option for these patients represents a significant clinical advance with the potential to improve their lives and change the course of disease.”

Data on capivasertib plus abiraterone and prednisone

The approval is supported by data from the phase 3 CAPItello-281 trial (NCT04493853), which met its primary end point by showing that the addition of capivasertib to abiraterone and prednisone significantly improved radiographic progression-free survival (rPFS) vs abiraterone and prednisone alone.² The median rPFS was 33.2 months in the treatment arm vs 25.7 months in the control arm (HR, 0.81; 95% CI, 0.66 to 0.98; P = .034). The rPFS benefit was observed across most prespecified subgroups and irrespective of disease risk and metastatic volume of disease.

The study included 1012 patients with PTEN-deficient mHSPC. Participants were randomly assigned 1:1 to receive capivasertib plus abiraterone (n = 507) vs placebo plus abiraterone (n = 505) with concomitant prednisone/prednisolone and androgen deprivation therapy (ADT). Baseline characteristics were well-balanced between both arms.

Related: Daniel George, MD, on capivasertib plus abiraterone in PTEN-deficient mHSPC

The OS results were immature at the time of report. The data showed a numerical improvement in OS with the capivasertib regimen, although the difference did not achieve statistical significance (HR, 0.90; 95% CI, 0.71 to 1.15; P = .401). The combination also demonstrated numerical improvements in other secondary end points such as time to first subsequent therapy (HR, 0.91; 95% CI, 0.75 to 1.11) and symptomatic skeletal event-free survival (HR, 0.82; 95% CI, 0.66 to 1.02). The capivasertib combination also showed clinically meaningful improvements in time to castration resistance (HR, 0.77; 95% CI, 0.63 to 0.94) and time to prostate-specific antigen progression (HR, 0.73; 95% CI, 0.52 to 1.01).

The most common adverse events (AEs) with the capivasertib regimen were diarrhea (51.9% vs 8.0% with placebo), hyperglycemia (38.0% vs 12.9% with placebo), and rash (35.4% vs 7.0% with placebo). Serious AEs were reported in 42.5% of patients in the capivasertib arm and 26.0% of patients in the placebo arm. Deaths attrubited to an AE occurred in 7.2% of patients in the treatment arm vs 5.2% of patients in the placebo arm.

REFERENCES

1. Truqap combination approved in the US as first and only targeted treatment for PTEN-deficient metastatic hormone-sensitive prostate cancer. News release. AstraZeneca. June 12, 2026. Accessed June 12, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/truqap-approved-in-us-for-prostate-cancer.html

2. Fizazi K, Clarke NW, Santis MD, et al. Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study. Ann Oncol. 2026;37(1):53-68. doi:10.1016/j.annonc.2025.10.004