AstraZeneca’s TRUQAP (capivasertib) in combination with abiraterone and prednisone has been approved in the US as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer, previously referred to as metastatic Hormone-Sensitive Prostate Cancer (mHSPC), as detected by a US Food and Drug Administration (FDA)-authorised test.

The approval by the US FDA was based on positive results from the CAPItello-281 phase 3 trial, presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in Annals of Oncology.

Daniel George, MD, Director of Genitourinary Oncology, Duke Cancer Institute and investigator for the CAPItello-281 trial, said, “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. 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.”

Results from the primary analysis of the CAPItello-281 phase 3 trial showed a statistically significant 19 percent reduction in the risk of radiographic disease progression or death and a clinically meaningful improvement in median radiographic Progression-Free Survival (rPFS) of 7.5 months with TRUQAP in combination with abiraterone and Androgen Deprivation Therapy (ADT) versus treatment with abiraterone and ADT with placebo (based on a Hazard Ratio [HR] of 0.81; 95 percent Confidence Interval [CI] 0.66-0.98; p=0.034). Median rPFS was 33.2 months for the TRUQAP combination versus 25.7 months for the comparator arm. While Overall Survival (OS) data were immature at the time of the primary analysis, results for OS numerically favored the TRUQAP combination versus the comparator arm. The trial will continue as planned to further assess OS as a key secondary endpoint.

Dave Fredrickson, Executive Vice President (EVP), Oncology Haematology Business Unit, AstraZeneca, said, “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. Today’s approval makes clear the importance of testing for actionable biomarkers, including PTEN deficiency, in prostate cancer.”

The safety profile of TRUQAP in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each medicine. Grade 3 or higher Adverse Events (AEs) occurred in 67 percent of patients treated with the TRUQAP combination, with rash (12.3 percent) and hyperglycemia (10.3 percent) the most frequently reported.

Concurrently, with this approval, the FDA also approved a companion diagnostic test to detect PTEN deficiency in tumors of patients with prostate adenocarcinoma.

A regulatory application for the TRUQAP combination in this setting is under review in the EU based on the CAPItello-281 phase 3 trial.