AstraZeneca recently announced positive results from the Phase 3 CAPItello-281 clinical trial. The analysis showed that in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC), Truqap (capivasertib) in combination with abiraterone and androgen deprivation therapy (ADT) resulted in a statistically significant and clinically meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS) compared with abiraterone and ADT plus placebo.
At the time of this analysis, overall survival (OS) data were immature; however, the Truqap combination therapy showed an early trend toward improved OS versus the placebo arm. The trial will continue as planned to further evaluate the key secondary endpoint of OS.
The safety profile of Truqap when administered in combination with abiraterone and ADT in the CAPItello-281 trial was generally consistent with the known safety profiles of each individual agent. AstraZeneca stated that the trial data will be presented at upcoming medical conferences and shared with global regulatory authorities.
In patients with metastatic castration-sensitive prostate cancer (mCSPC), prostate cancer cells require high levels of androgens to drive cancer growth. Hormonal therapies such as ADT are now widely used to block the effects of male sex hormones and reduce androgen levels in the body. However, resistance to these therapies is common, creating a need to expand treatment options to delay disease progression and the emergence of castration resistance, a condition in which prostate cancer continues to grow and spread to other parts of the body despite such treatments.
In patients with newly diagnosed mHSPC, the cancer has spread to distant parts of the body at initial diagnosis. PTEN loss or deficiency promotes cancer cell growth, leads to dysregulation of the PI3K/AKT pathway, and is associated with poor prognosis in patients with prostate cancer.
Truqap is an oral, selective ATP-competitive inhibitor that suppresses all three isoforms of the serine/threonine kinase AKT (AKT 1/2/3). The agent is designed to act by targeting AKT1 gene mutations, which drive tumour growth and proliferation.
According to the press release, Truqap plus abiraterone and androgen deprivation therapy (ADT) is the first AKT inhibitor combination proven to benefit this specific subtype of prostate cancer.
Based on positive results from the Phase 3 CAPItello-291 trial, Truqap was approved by the U.S. FDA in November last year for use in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. Beyond the United States, the therapy is also approved for this same indication in the European Union, Japan and Australia.
Truqap is currently being evaluated in multiple Phase 3 trials assessing its use in combination with existing therapies for breast cancer (the CAPItello-292S trial) and prostate cancer (the CAPItello-280 trial and the CAPItello-281 trial).
