Game-changer for prostate cancer? AstraZeneca’s Truqap shows remarkable results in pivotal trial

AstraZeneca has announced results from its CAPItello-281 Phase III trial, revealing that Truqap (capivasertib), when combined with abiraterone and androgen deprivation therapy (ADT), significantly improves radiographic progression-free survival (rPFS) in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC). This marks the first success for an AKT inhibitor combination in this aggressive cancer subtype, setting a potential new benchmark for treatment options.

The trial involved patients with PTEN-deficient de novo mHSPC, a particularly challenging subset of prostate cancer known for its poor prognosis. Investigators noted that Truqap, in combination with abiraterone and ADT, delivered statistically significant improvements in delaying cancer progression compared to standard therapy with placebo. While data on overall survival (OS) remains immature, early trends suggest a potential survival benefit, which will be further assessed as the trial progresses.

Addressing unmet needs in metastatic prostate cancer

Prostate cancer remains the second most common cancer in men and the fifth leading cause of male cancer-related deaths worldwide. Each year, more than 200,000 men are diagnosed with mHSPC, with approximately one in four of these patients presenting with PTEN-deficient tumours. PTEN loss, which disrupts the PI3K/AKT pathway, fuels aggressive cancer growth and significantly worsens survival outcomes.

Hormone-sensitive prostate cancer, which initially responds to therapies that lower androgen levels, often develops resistance, leading to castration-resistant prostate cancer. With limited treatment options available for PTEN-deficient mHSPC, the findings from CAPItello-281 provide a vital step forward in addressing this gap.

Dr Karim Fizazi, a principal investigator for the study, explained that patients with PTEN-deficient tumours face limited treatment options and poor survival rates. He noted that the addition of capivasertib to standard therapies represents a meaningful advancement in improving outcomes for this patient group.

A milestone in AKT inhibitor development

Truqap, a first-in-class AKT inhibitor, was developed to target all three AKT isoforms. This innovative approach addresses a key driver of prostate cancer progression in patients with PTEN-deficient tumours. Administered in an intermittent dosing schedule (four days on, three days off), the drug has demonstrated both efficacy and tolerability in various clinical trials.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, emphasised the significance of these results, stating that the trial is the first to show how adding an AKT inhibitor to standard care can benefit patients with biomarker-driven prostate cancer. She highlighted the need for continued research to confirm the observed overall survival trends and ensure this therapy’s long-term benefits.

Looking ahead

The CAPItello-281 trial enrolled over 1,000 patients globally and focused on de novo mHSPC cases with confirmed PTEN deficiency. rPFS was the primary endpoint, while OS was designated as a key secondary measure. The safety profile of Truqap, combined with abiraterone and ADT, aligned with previous studies, showing no unexpected adverse events.

AstraZeneca intends to share these findings with global regulatory authorities and present detailed data at an upcoming medical conference. The company also continues to evaluate Truqap in multiple Phase III trials for other indications, including breast and prostate cancers.

potential implications for prostate cancer treatment

The positive results from CAPItello-281 highlight the growing importance of personalised medicine in oncology. By targeting specific biomarkers such as PTEN deficiency, Truqap exemplifies how innovative therapies can address unmet needs in difficult-to-treat cancers. Should regulatory approvals follow, this therapy could redefine treatment standards for patients with PTEN-deficient mHSPC, offering hope for improved survival outcomes in a historically challenging cancer subtype.