FDA Approves Capivasertib Plus Abiraterone and Prednisone for PTEN-Deficient mHSPC

The FDA has approved capivasertib (Truqap) in combination with abiraterone and prednisone for the treatment of adult patients with PTEN-deficient metastatic androgen pathway modulation–naive or sensitive (mAPMN/S) prostate cancer (previously metastatic hormone-sensitive prostate cancer [mHSPC]), as detected by an FDA-authorized test.¹

The FDA concurrently approved a companion diagnostic test for the detection of PTEN deficiency in the tumors of patients who have prostate adenocarcinoma.

These regulatory decisions were backed by data from the phase 3 CAPItello-281 trial (NCT04493853), which were presented at the 2025 ESMO Congress and simultaneously published in Annals of Oncology. In the trial’s overall population, patients who received capivasertib plus abiraterone and androgen deprivation therapy (ADT; n = 507) achieved a statistically significant reduction in the risk of radiographic disease progression or death, as well as a clinically meaningful improvement in median radiographic progression-free survival (rPFS), vs placebo plus abiraterone and ADT (n = 505). The median rPFS was 33.2 months (95% CI, 25.8-44.2) with the capivasertib-based regimen vs 25.7 months (95% CI, 22.0-29.9) with the control regimen (HR, 0.81; 95% CI, 0.66-0.98; P = .034).^1,2 In the population of patients with 100% PTEN deficiency, the median rPFS was 34.1 months (95% CI, 22.1-not calculable) in the capivasertib arm (n = 169) vs 22.1 months (95% CI, 14.7-26.5) in the control arm (HR, 0.68; 95% CI, 0.48-0.96).²

Although the overall survival (OS) data were not mature at the time of the primary analysis, the OS outcomes numerically favored the capivasertib arm.¹ The OS assessment will continue.

Additionally, the safety profile of the capivasertib-containing regimen was deemed consistent with the known safety profiles of each agent. In total, 67% of patients in the investigational arm experienced grade 3 or higher adverse effects, with rash (12.3%) and hyperglycemia (10.3%) as the most commonly seen.

“Patients with PTEN-deficient mHSPC, now called mAPMN/S prostate cancer, experience faster progression and worse prognosis than those without PTEN deficiency,” Daniel George, MD, director of Genitourinary Oncology at Duke Cancer Institute in Durham, North Carolina, and an investigator for the CAPItello-281 trial, stated in a news release. “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.”

What was the design of the CAPItello-281 trial?

This double-blind, randomized trial enrolled 1012 adult patients with histologically confirmed, PTEN-deficient, newly diagnosed APMN/S prostate adenocarcinoma. PTEN deficiency was confirmed by central testing.

The primary end point was investigator-assessed rPFS. OS served as a key secondary end point.

What are the next steps for using and further developing capivasertib in prostate cancer?

“CAPItello-281 showed that for the first time, we can target a key driver of this disease to bring meaningful benefit to the 1 in 4 patients with this form of prostate cancer who urgently need biomarker-directed therapies,” Dave Fredrickson, executive vice president of the Oncology Haematology Business Unit at AstraZeneca, added in the news release. “Today’s approval makes clear the importance of testing for actionable biomarkers, including PTEN deficiency, in prostate cancer.”

A regulatory application for capivasertib plus abiraterone and ADT for the treatment of patients with PTEN-deficient metastatic androgen pathway modulation–naive or sensitive mAPMN/S prostate cancer is under review in the EU, also based on the results of CAPItello-281.

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