On June 12, 2026, the U.S. Food and Drug Administration approved capivasertib, marketed as Truqap by AstraZeneca, in combination with abiraterone and prednisone for adults with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer that is PTEN-deficient, as detected by an FDA-authorized test.
Metastatic androgen pathway modulation-naïve or -sensitive prostate cancer was previously referred to as metastatic hormone-sensitive prostate cancer. According to AstraZeneca, this approval makes capivasertib plus abiraterone and prednisone the first and only targeted treatment approved in the United States for this specific PTEN-deficient mAPMN/S prostate cancer population.
The FDA also approved the VENTANA PTEN (SP218) RxDx Assay, developed by Ventana Medical Systems/Roche Diagnostics, as a companion diagnostic to identify patients with PTEN-deficient prostate cancer who may be eligible for treatment with capivasertib.
PTEN-Deficient Prostate Cancer
PTEN deficiency is associated with dysregulation of the PI3K/AKT pathway and has been linked to more aggressive prostate cancer biology and poorer outcomes. AstraZeneca noted that approximately one in four patients with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer have PTEN-deficient tumors. PTEN deficiency can be identified by immunohistochemistry testing at the time of diagnosis.
Read more about Prostate Cancer Cure Rate on OncoDaily.
CAPItello-281
The approval was supported by CAPItello-281, a randomized, double-blind, placebo-controlled, multicenter Phase 3 trial that enrolled 1,012 adults with newly diagnosed, PTEN-deficient metastatic androgen pathway modulation-naïve or -sensitive prostate cancer.
According to AstraZeneca, the trial results were presented at the 2025 European Society for Medical Oncology Congress and published in Annals of Oncology. Tumor PTEN deficiency was prospectively assessed by central testing using the immunohistochemistry-based VENTANA PTEN (SP218) RxDx Assay. PTEN deficiency was defined as at least 90% of viable malignant cells showing no specific cytoplasmic staining.
Patients were randomized 1:1 to receive either capivasertib plus abiraterone or placebo plus abiraterone. Abiraterone was administered with prednisone or prednisolone. The major efficacy outcome measure was investigator-assessed radiographic progression-free survival. Overall survival was included as an additional efficacy outcome measure.
Key Results
CAPItello-281 showed a statistically significant improvement in radiographic progression-free survival with capivasertib plus abiraterone compared with placebo plus abiraterone. Median radiographic progression-free survival was 33.2 months in the capivasertib arm, with a 95% confidence interval of 25.8 to 44.2, compared with 25.7 months in the placebo arm, with a 95% confidence interval of 22.0 to 29.9.
The hazard ratio was 0.81, with a 95% confidence interval of 0.66 to 0.98 and a two-sided p-value of 0.034. According to AstraZeneca, this corresponded to a 19% reduction in the risk of radiographic disease progression or death.
Overall survival data were immature at the time of the radiographic progression-free survival analysis. Overall survival results numerically favored the capivasertib combination, and the trial will continue to further assess overall survival as a key secondary endpoint.
Safety
The prescribing information includes warnings and precautions for hyperglycemia, diarrhea, cutaneous adverse reactions, and embryo-fetal toxicity. The safety profile of capivasertib in combination with abiraterone and androgen deprivation therapy in CAPItello-281 was broadly consistent with the known profile of each medicine.
Grade 3 or higher adverse events occurred in 67% of patients treated with the capivasertib combination. The most frequently reported Grade 3 or higher adverse events were rash, reported in 12.3% of patients, and hyperglycemia, reported in 10.3%.
Results From ASCO GU 2026
Additional CAPItello-281 data presented at ASCO GU 2026 evaluated patient-reported outcomes and tolerability with capivasertib plus abiraterone in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer.
Overall health-related quality of life was generally maintained with capivasertib, with no clinically meaningful differences between treatment arms in FACT-P total score, physical wellbeing, or functional wellbeing. Time to deterioration in physical wellbeing occurred earlier with capivasertib, with a hazard ratio of 1.43 and a 95% confidence interval of 1.15 to 1.78.
Adverse events associated with AKT inhibition were more frequent with capivasertib, including diarrhea, rash, and hyperglycemia. Diarrhea occurred in 51.9% of patients receiving capivasertib versus 8.0% with placebo, rash in 35.4% versus 7.0%, and hyperglycemia in 38.0% versus 12.9%.
Overall, the ASCO GU data showed that patient-reported quality of life remained generally stable, although diarrhea, rash, and hyperglycemia were more common with capivasertib.
Read more about CAPItello-281 Trial at ASCO GU on OncoDaily.
What Is Truqap?
Truqap, also known as capivasertib, is a first-in-class oral AKT inhibitor that targets AKT1, AKT2, and AKT3. In this approval, it is used with abiraterone and prednisone for adults with PTEN-deficient metastatic androgen pathway modulation-naïve or -sensitive prostate cancer.
Recommended Dosage
The recommended capivasertib dose is 400 mg orally twice daily, approximately 12 hours apart, with or without food, for 4 days followed by 3 days off. Treatment is continued until disease progression or unacceptable toxicity. The recommended abiraterone acetate dose is 1000 mg once daily in combination with prednisone 5 mg once daily. Patients receiving capivasertib and abiraterone acetate should also receive a GnRH analog concurrently or should have had bilateral orchiectomy.
Expert Highlights
Daniel George, MD, Director of Genitourinary Oncology at 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.”
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.”
Takeaway
With this approval, adults with PTEN-deficient metastatic androgen pathway modulation-naïve or -sensitive prostate cancer gain their first biomarker-directed treatment option. The approval is supported by CAPItello-281, where capivasertib plus abiraterone improved radiographic progression-free survival compared with placebo plus abiraterone in patients with PTEN-deficient disease.