FDA approves Truqap plus abiraterone for PTEN‑deficient metastatic prostate cancer, first targeted therapy for this biomarker‑defined subgroup.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved AstraZeneca’s Truqap (capivasertib) in combination with abiraterone, prednisone, and androgen deprivation therapy (ADT) for adults with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer. The approval makes Truqap the first and only targeted therapy specifically indicated for this biomarker-defined subgroup of metastatic hormone-sensitive prostate cancer.
The decision is based on findings from the Phase III CAPItello-281 trial, which showed that adding the AKT inhibitor to standard therapy significantly delayed disease progression in patients with PTEN-deficient tumors, an aggressive form of prostate cancer associated with poor clinical outcomes.
Targeting a Key Driver of Aggressive Prostate Cancer
Prostate cancer remains the second most commonly diagnosed cancer in men worldwide, with more than 1.4 million new cases annually. Among patients with metastatic hormone-sensitive disease, approximately one in four harbor PTEN-deficient tumors.
PTEN is a tumor suppressor gene that regulates the PI3K/AKT signaling pathway. Loss of PTEN function leads to uncontrolled activation of AKT signaling, promoting tumor growth, disease progression, and treatment resistance. Patients with PTEN-deficient metastatic prostate cancer typically experience faster progression and worse survival outcomes than those without the alteration.
Truqap is a first-in-class, oral ATP-competitive inhibitor that blocks all three AKT isoforms (AKT1, AKT2, and AKT3), directly targeting a central driver of disease biology in PTEN-deficient tumors.
CAPItello-281 Demonstrated Significant Progression-Free Survival Benefit
CAPItello-281 (NCT04493853) was a global, randomized, double-blind Phase III trial that enrolled 1,012 patients with newly diagnosed PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive prostate adenocarcinoma confirmed through centralized testing.
The study evaluated Truqap plus abiraterone and ADT against placebo plus abiraterone and ADT. The primary endpoint was radiographic progression-free survival (rPFS), with overall survival (OS) assessed as a key secondary endpoint.
At the primary analysis, the Truqap combination reduced the risk of radiographic disease progression or death by 19% compared with the control arm (HR 0.81; 95% CI: 0.66–0.98; p=0.034).
Median rPFS reached 33.2 months in the Truqap arm versus 25.7 months with standard treatment alone, representing a clinically meaningful improvement of 7.5 months.
Although overall survival data remain immature, an early numerical trend favored the Truqap regimen. The study will continue to evaluate survival outcomes as follow-up matures.
Safety Profile Consistent with Previous Experience
The safety findings were broadly consistent with the established profile of capivasertib and the accompanying therapies.
Grade 3 or higher adverse events occurred in 67% of patients receiving the Truqap combination. The most common severe treatment-related toxicities were rash (12.3%) and hyperglycemia (10.3%). No new safety signals were identified during the study.
Alongside the drug approval, the FDA also authorized a companion diagnostic test to identify PTEN deficiency in prostate adenocarcinoma tumors, enabling biomarker-guided patient selection.
Expanding Precision Medicine in Prostate Cancer
The approval introduces the first biomarker-directed treatment strategy for PTEN-deficient metastatic prostate cancer, a subgroup known to progress more rapidly and carry a poorer prognosis.
Daniel George, MD, Director of Genitourinary Oncology at Duke Cancer Institute and a CAPItello-281 investigator, noted that delaying disease progression remains a major priority for these patients and said the approval provides an important new targeted treatment option.
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, highlighted that CAPItello-281 demonstrated the ability to target a key driver of PTEN-deficient disease and reinforced the importance of routine biomarker testing to identify eligible patients.
A regulatory application for the combination is currently under review in Europe, while broader development of capivasertib continues across multiple oncology settings, including earlier-line breast cancer in the Phase III CAPItello-292 trial.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.