Promising outcomes from the CAPItello-281 phase III study reveal that AstraZeneca’s Truqap (capivasertib) alongside abiraterone and androgen deprivation therapy (ADT) yielded a statistically significant and clinically notable enhancement in radiographic progression-free survival (rPFS) compared to abiraterone and ADT with a placebo in individuals with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC).
At the time of this analysis, overall survival (OS) data remained immature, though there was an early indication of potential OS improvement with the Truqap combination versus abiraterone and ADT with a placebo. The trial will persist as planned to deepen the assessment of OS as a critical secondary metric.
Prostate cancer ranks as the second most common cancer among men and is the fifth leading cause of male cancer mortality worldwide. Only about a third of patients with metastatic prostate cancer survive five years post-diagnosis. Newly detected mHSPC is an aggressive variant of the disease, characterized by unfavorable outcomes and survival rates. Every year, approximately 200,000 cases of mHSPC are diagnosed, with a quarter exhibiting PTEN-deficient tumors. Tumors with PTEN deficiency exhibit especially poor prognoses.
Principal investigator for the trial, Dr. Karim Fizazi from Institut Gustave Roussy, affirmed: “Patients facing this aggressive prostate cancer type with PTEN deficiency currently encounter dire prognoses, underscoring a dire need for advanced treatments that exceed contemporary therapies. The results observed with capivasertib in combination with abiraterone-prednisone and androgen deprivation therapy in the CAPItello-281 trial signify progress for these patients.”
Susan Galbraith, EVP, oncology R&D at AstraZeneca, added: “These groundbreaking results demonstrate for the first time that merging an AKT inhibitor with standard-of-care therapy extends benefits to patients with PTEN-deficient metastatic hormone-sensitive prostate cancer. By targeting a core disease driver, we have enhanced current therapies and showcased this combination’s potential in a critical unmet need area. Monitoring maturity in key secondary endpoints, including overall survival, will be vital.”
The safety profile of Truqap with abiraterone and ADT in CAPItello-281 aligned with known profiles of each medicine.
Data are planned for presentation at an upcoming medical conference and will be communicated with global regulatory bodies.
Prostate cancer holds the distinction of being the second most common cancer in men and is the fifth leading cause of cancer deaths among men worldwide, with an incidence exceeding 1.4 million and around 397,000 deaths in 2022.
Metastatic prostate cancer presents a significant mortality rate, with just one-third surviving five years post-diagnosis. Prostate cancer development is mainly driven by male sex hormones, or androgens, including testosterone.
In patients suffering from metastatic hormone-sensitive prostate cancer (also termed metastatic castration-sensitive prostate cancer), androgens are crucial for cancer progression. Hormonal therapies like ADT are frequently employed to block androgen effects and reduce their levels within the body. However, resistance development to these therapies is common, necessitating breakthroughs to extend their utility to delay disease progression and prevent castration resistance, where the cancer continues spreading despite therapy.
In de novo mHSPC patients, the cancer migrates to distant body parts upon initial diagnosis.
PTEN loss or deficiency fosters cancer cell proliferation by disrupting the PI3K/AKT pathway, correlating with poor outcomes in prostate cancer patients.
The CAPItello-281 study is a phase III, double-blind, randomized assessment comparing the efficacy and safety of Truqap with abiraterone and ADT against abiraterone and ADT with a placebo in treating PTEN-deficient de novo mHSPC patients.
Recruiting 1,012 adult participants with histologically affirmed de novo hormone-sensitive prostate adenocarcinoma and PTEN deficiency verified by centralized testing, the primary endpoint of CAPItello-281 is rPFS evaluated by the investigator, with OS as an additional outcome measure.
Truqap operates as a pioneering, potent, ATP-competitive inhibitor targeting all three AKT isoforms (AKT1/2/3), administered as 400mg doses twice daily in an intermittent fashion (four days on, three days off), chosen in earlier trials due to tolerability and target inhibition degree.
Presently approved in the US, EU, Japan, and multiple countries for HR-positive (or ER-positive), HER2-negative locally advanced or metastatic breast cancer patients with one or more biomarker alterations (PIK3CA, AKT1, or PTEN) following progression post-endocrine regimen as per CAPItello-291 trial outcomes, Truqap is also sanctioned in Australia for HR-positive, HER2-negative locally advanced or metastatic breast cancer treatments.
Currently, Truqap undergoes evaluation in phase III trials addressing breast cancer (CAPItello-292) and prostate cancer (CAPItello-280, CAPItello-281) in unison with reputable treatments.
Truqap originated from AstraZeneca following a collaboration with Astex Therapeutics, partnering with the Institute of Cancer Research and Cancer Research Technology Limited.
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