AstraZeneca's capivasertib (Truqap) in combination with abiraterone acetate (Zytiga) and androgen deprivation therapy (ADT) has demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared to placebo plus abiraterone and ADT in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC). These topline results come from the phase 3 CAPItello-281 trial (NCT04493853).
The global trial enrolled 1,012 adult patients with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency. Patients were randomly assigned 1:1 to receive either 400 mg capivasertib twice daily on days 1 to 4 of a 28-day cycle or a matching placebo, in combination with 1000 mg abiraterone daily plus ADT. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was rPFS, assessed for up to approximately 55 months. Secondary endpoints included overall survival (OS), time to the start of first subsequent therapy, symptomatic skeletal event-free survival, and time to pain progression, among other measures.
Clinical Impact and Expert Commentary
Principal investigator Karim Fizazi, MD, PhD, from Institut Gustave Roussy and University of Paris Saclay, noted the poor prognosis faced by patients with PTEN-deficient prostate cancer and the urgent need for new treatments. "The results seen with capivasertib in combination with abiraterone-prednisone and androgen deprivation therapy in the CAPItello-281 trial represent a step forward for these patients," he stated in a news release.
Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, emphasized that these results demonstrate, "for the first time, that adding an AKT inhibitor to a standard-of-care therapy can provide benefit to patients with a biomarker of PTEN-deficient metastatic hormone-sensitive prostate cancer." She further added, "By targeting a key driver of the disease, we have been able to improve upon current therapies and demonstrate the potential role of this combination in an area of critical unmet need."
Understanding PTEN Deficiency in mHSPC
Metastatic hormone-sensitive prostate cancer (mHSPC) requires high levels of androgens to fuel cancer growth. Approximately 200,000 patients are diagnosed with mHSPC each year, and one in four have PTEN-deficient tumors. PTEN loss or deficiency fuels the growth of cancer cells, leading to dysregulation of the PI3K/AKT pathway, and is associated with poor outcomes in patients with prostate cancer.
Safety and Further Studies
The safety profile of TRUQAP in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each medicine. AstraZeneca reported that OS data were immature at the time of the report, though there was a trend toward improvement. The trial is ongoing to assess this secondary endpoint. Full data will be presented at an upcoming medical meeting and shared with global regulatory authorities.
Capivasertib is also being studied in the phase 3 CAPItello-280 trial in combination with docetaxel versus placebo plus docetaxel in patients with metastatic castration-resistant prostate cancer. Completion of this study is expected in December 2026.
