FDA Approves AstraZeneca’s Truqap Combination for PTEN-Deficient Metastatic Prostate Cancer

FDA Approves AstraZeneca’s Truqap Combination for PTEN-Deficient Metastatic Prostate Cancer

On June 12, 2026, the U.S. Food and Drug Administration (FDA) approved AstraZeneca’s Truqap (capivasertib) in combination with abiraterone and prednisone as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer—historically referred to as metastatic hormone-sensitive prostate cancer (mHSPC). Concurrently, the FDA approved a companion diagnostic test to identify PTEN deficiency in tumor tissue at the time of diagnosis.¹

Clinical Efficacy and the CAPItello-281 Study

The approval is based on positive results from the global, double-blind, randomized Phase 3 CAPItello-281 trial, which evaluated Truqap in combination with abiraterone and androgen deprivation therapy (ADT) versus placebo plus abiraterone and ADT in 1,012 adult patients with newly diagnosed, histologically confirmed PTEN-deficient prostate cancer.

• Radiographic PFS Win: Truqap demonstrated a statistically significant 19% reduction in the risk of radiographic disease progression or death (Hazard Ratio [HR] of 0.81; 95% Confidence Interval [CI] 0.66–0.98; p=0.034).
• Extension of Remission: The median radiographic progression-free survival (rPFS) was 33.2 months in the Truqap combination arm compared to 25.7 months in the comparator arm—a clinically meaningful improvement of 7.5 months.
• Overall Survival (OS): While the OS data were immature at the time of the primary analysis, results numerically favored the Truqap combination. The trial is ongoing to further evaluate OS as a key secondary endpoint.
• Safety Profile: Grade 3 or higher adverse events occurred in 67% of patients on the Truqap combination. The most frequently reported high-grade toxicities were rash (12.3%) and hyperglycemia (10.3%), which are consistent with the known pharmacodynamic effects of AKT class inhibition.

Clinical Significance of PTEN Deficiency

Prostate cancer is the second most common cancer in men worldwide. Approximately 200,000 patients globally (including 35,000 in the United States) are diagnosed with mAPMN/S prostate cancer each year. Roughly one in four of these patients have PTEN-deficient tumors. PTEN loss or deficiency leads to hyperactivation of the PI3K/AKT cell-signaling pathway, which fuels rapid tumor growth and resistance to standard hormonal therapies. PTEN deficiency represents an independent risk factor associated with aggressive disease progression, rapid castration resistance, and poor clinical outcomes. Truqap—a first-in-class, oral, potent adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3)—directly targets this oncogenic driver.²

Verbatim Quotes

From AstraZeneca’s official press release on June 12, 2026:

"AstraZeneca’s Truqap (capivasertib) in combination with abiraterone and prednisone has been approved in the US as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer, previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC)..."

Daniel George, MD, Director of Genitourinary Oncology at Duke Cancer Institute and investigator for the CAPItello-281 trial:

“Patients with PTEN-deficient metastatic hormone-sensitive prostate cancer... experience faster progression and worse prognosis than those without PTEN deficiency. Keeping patients with this form of prostate cancer in remission and free from disease progression as long as possible is a high priority. Today’s landmark approval of the capivasertib combination as the first and only targeted treatment option for these patients represents a significant clinical advance...”