AstraZeneca's Truqap (capivasertib), when combined with abiraterone and androgen deprivation therapy (ADT), has demonstrated a statistically significant improvement in radiographic progression-free survival (rPFS) in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC). The findings come from the Phase III CAPItello-281 trial, a double-blind, randomised study, and mark a potential advancement in treating this aggressive form of prostate cancer.
The CAPItello-281 trial enrolled 1,012 adult patients with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency. The primary endpoint was rPFS, assessed by investigators, with overall survival (OS) as a key secondary endpoint. Patients were treated with either Truqap plus abiraterone and ADT, or placebo plus abiraterone and ADT.
The safety profile of Truqap in combination with abiraterone and ADT was broadly consistent with the known profile of each medicine.
Significance of the Results
Metastatic hormone-sensitive prostate cancer requires high levels of androgens to fuel cancer growth. Hormone therapies like ADT are commonly used to block the action of male sex hormones, but resistance to these therapies is common. Extending the effectiveness of these therapies is crucial to delay disease progression and castration resistance. PTEN loss or deficiency further exacerbates the condition by dysregulating the PI3K/AKT pathway, leading to poorer outcomes.
Prostate cancer is a significant global health concern, being the second most prevalent cancer in men and the fifth leading cause of male cancer death worldwide. In 2022, there were over 1.4 million new cases and approximately 397,000 deaths. Metastatic prostate cancer carries a high mortality rate, with only about one-third of patients surviving five years post-diagnosis.
About Truqap
Truqap (capivasertib) is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). It is administered at 400mg twice daily on an intermittent dosing schedule of four days on and three days off, based on tolerability and target inhibition observed in early-phase trials. Truqap is already approved in the US, EU, Japan, and Australia for HR-positive, HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations (PIK3CA, AKT1, or PTEN) after endocrine-based regimen failure, based on the CAPItello-291 trial results.
AstraZeneca is also evaluating Truqap in Phase III trials for breast cancer (CAPItello-292) and other prostate cancer settings (CAPItello-280).
Data from the CAPItello-281 trial will be presented at a forthcoming medical meeting and shared with global regulatory authorities.
