AstraZeneca's Truqap (capivasertib), in combination with abiraterone and androgen deprivation therapy (ADT), has demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC). The findings come from the Phase III CAPItello-281 trial, potentially offering a new treatment avenue for this aggressive form of prostate cancer.
The global trial enrolled 1,012 adult patients with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency. The study compared Truqap in combination with abiraterone and ADT versus abiraterone and ADT with placebo. The primary endpoint was rPFS, assessed by investigator review.
CAPItello-281 Trial Results
The CAPItello-281 trial results indicated that the Truqap combination significantly prolonged rPFS compared to the placebo arm. While overall survival (OS) data were immature at the time of this analysis, an early trend towards OS improvement was observed in the Truqap arm. The trial is ongoing to further evaluate OS as a key secondary endpoint.
Karim Fizazi, MD, PhD, from Institut Gustave Roussy, highlighted the urgent need for new treatments for patients with PTEN-deficient prostate cancer, noting the results of the CAPItello-281 trial as a "step forward" for these patients.
Addressing Unmet Needs in mHSPC
Metastatic hormone-sensitive prostate cancer is an aggressive disease with poor outcomes. Approximately 200,000 patients are diagnosed with mHSPC each year, and one in four have PTEN-deficient tumors, which are associated with a particularly poor prognosis. Current hormone therapies, such as ADT, are used to block the action of male sex hormones, but resistance to these therapies is common.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, emphasized that the CAPItello-281 data shows that targeting a key driver of prostate cancer with an AKT inhibitor can improve upon current therapies. "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," she stated.
Truqap: A First-in-Class AKT Inhibitor
Truqap (capivasertib) is a first-in-class, potent, 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. Truqap is already approved in the US, EU, Japan, and other countries for HR-positive, HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations.
Safety Profile
The safety profile of Truqap in combination with abiraterone and ADT in the CAPItello-281 trial was broadly consistent with the known profiles of each medicine. Full data from the trial will be presented at an upcoming medical meeting and shared with global regulatory authorities.
