Wilmington, Del. — AstraZeneca said the U.S. Food and Drug Administration has approved TRUQAP in combination with abiraterone and prednisone as the first targeted treatment for adults with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive prostate cancer.
The condition was previously referred to as metastatic hormone-sensitive prostate cancer. The treatment is approved for patients whose disease is detected by an FDA-authorized test.
TRUQAP, also known as capivasertib, is a first-in-class AKT inhibitor. AstraZeneca said the approval marks the drug’s expansion into a second tumor type and addresses an aggressive form of prostate cancer associated with poor prognosis.
The FDA approval was based on results from the CAPItello-281 Phase III trial, which were presented at the 2025 European Society for Medical Oncology Congress and published in Annals of Oncology.
Prostate cancer is the second most prevalent cancer in men and the fifth leading cause of male cancer death globally, with more than 1.4 million people diagnosed each year. About 200,000 patients worldwide, including 35,000 in the United States, are diagnosed annually with metastatic androgen pathway modulation-naïve or sensitive prostate cancer, according to AstraZeneca.
The company said one in four of these patients have PTEN-deficient tumors, which can fuel cancer cell growth and define an aggressive form of the disease associated with poor outcomes. PTEN deficiency can be identified by immunohistochemistry testing at diagnosis.
“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,” said Daniel George, MD, Director of Genitourinary Oncology at Duke Cancer Institute and investigator for the CAPItello-281 trial.
Dave Fredrickson, Executive Vice President, 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 one in four 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.”
Results from the primary analysis of CAPItello-281 showed a statistically significant 19% reduction in the risk of radiographic disease progression or death and a clinically meaningful improvement in median radiographic progression-free survival of 7.5 months with TRUQAP in combination with abiraterone and androgen deprivation therapy, compared with abiraterone and androgen deprivation therapy with placebo.
Median radiographic progression-free survival was 33.2 months for the TRUQAP combination, compared with 25.7 months for the comparator arm. Overall survival data were immature at the time of the primary analysis, but results numerically favored the TRUQAP combination. The trial will continue to further assess overall survival as a key secondary endpoint.
AstraZeneca said the safety profile of TRUQAP in combination with abiraterone and androgen deprivation therapy was broadly consistent with the known profile of each medicine. Grade 3 or higher adverse events occurred in 67% of patients treated with the TRUQAP combination, with rash and hyperglycemia the most frequently reported.
Alongside the 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 European Union based on the CAPItello-281 Phase III trial.
