Truqap improves radiographic progression-free survival in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 Phase III trial

A significant breakthrough in the treatment of a specific subtype of prostate cancer has been achieved with AstraZeneca's new drug combination. On November 25, 2024, AstraZeneca announced positive top-line results from the CAPItello-281 Phase III trial. The trial demonstrated that Truquap (capivasertib), when combined with abiraterone and androgen deprivation therapy (ADT), significantly improved radiographic progression-free survival (rPFS) in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC), compared to abiraterone and ADT with a placebo.

The CAPItello-281 trial results mark a milestone as Truquap is the first and only AKT inhibitor combination to show benefit in this challenging subtype of prostate cancer. Although overall survival (OS) data were not yet mature at the time of this analysis, there were early signs that the Truquap combination might improve OS compared to the placebo group. The study will continue to monitor OS as a critical secondary endpoint.

Prostate cancer ranks as the second most common cancer in men and the fifth leading cause of cancer-related death among men worldwide. Metastatic prostate cancer has a grim prognosis, with only about one-third of patients surviving five years post-diagnosis. Newly diagnosed mHSPC is particularly aggressive and has poor outcomes. Approximately 200,000 new cases of mHSPC are diagnosed annually, with about a quarter of these patients exhibiting PTEN-deficient tumors. Patients with PTEN deficiency face an especially dire prognosis.

Dr. Karim Fizazi, the principal investigator of the trial and a prominent oncologist from Institut Gustave Roussy and University of Paris Saclay, emphasized the urgent need for better treatments for patients with PTEN-deficient prostate cancer. He highlighted the promising results of the CAPItello-281 trial, noting that the combination of capivasertib with abiraterone and ADT provided a significant advancement for these patients.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, expressed optimism about the trial results. She noted that this marks the first instance where an AKT inhibitor has been added to standard therapy, showing benefits for patients with PTEN-deficient mHSPC. Galbraith emphasized the importance of targeting critical disease drivers and improving current treatment regimens.

The safety profile of Truquap in combination with abiraterone and ADT was in line with the known safety profiles of the individual drugs. Detailed data from the trial will be presented at an upcoming medical conference and shared with global regulatory bodies.

CAPItello-281 is a double-blind, randomized Phase III trial conducted globally, involving 1,012 adult patients with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency. The primary focus of the trial was rPFS, with OS as a secondary endpoint.

Truquap, a potent inhibitor of all three AKT isoforms (AKT1/2/3), is administered on an intermittent dosing schedule of four days on and three days off, ensuring tolerability and effective target inhibition. Truquap is already approved in several countries for treating HR-positive, HER2-negative locally advanced or metastatic breast cancer with specific biomarker alterations.

This drug is undergoing evaluation in various Phase III trials for treating breast and prostate cancers in combination with established treatments. Truquap was discovered by AstraZeneca in collaboration with Astex Therapeutics and other research institutions.

AstraZeneca continues to lead innovations in oncology with a goal of finding cures for various forms of cancer. The company is committed to understanding the complexities of cancer and developing transformative medicines that can potentially change medical practices and improve patient experiences. AstraZeneca's ambition is to redefine cancer care and ultimately eliminate cancer as a cause of death.