FDA Approves Capivasertib (Truqap) Combo as First Targeted Therapy for PTEN-Deficient Prostate Cancer

FDA Approves Capivasertib (Truqap) Combo as First Targeted Therapy for PTEN-Deficient Prostate Cancer

On June 12, 2026, the U.S. Food and Drug Administration (FDA) approved AstraZeneca's first-in-class AKT inhibitor, Truqap (capivasertib), in combination with abiraterone and prednisone (along with androgen deprivation therapy - ADT).

This regimen is indicated as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer—the clinical state previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC).

Clinical Evidence from CAPItello-281

The approval was supported by positive results from the global Phase 3 CAPItello-281 trial (NCT04493853), which enrolled 1,012 patients with newly diagnosed, histologically confirmed mAPMN/S prostate adenocarcinoma and central laboratory-confirmed PTEN deficiency.

• Primary Endpoint: The Truqap combination demonstrated a statistically significant and clinically meaningful 19% reduction in the risk of radiographic disease progression or death compared to the placebo arm (Hazard Ratio [HR] of 0.81; 95% confidence interval [CI]: 0.66–0.98; p=0.034).
• Radiographic Progression-Free Survival (rPFS): Median rPFS was 33.2 months for the Truqap combination versus 25.7 months for the control group, representing a 7.5-month improvement.
• Overall Survival (OS): OS data were immature at the time of the primary analysis but numerically favored the Truqap arm. The trial will continue to follow patients to 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 common related toxicities were rash (12.3%) and hyperglycemia (10.3%), which are class-related effects of AKT pathway inhibition. Truqap is dosed intermittently on an active schedule of four days on, three days off to maximize tolerability.

The Role of PTEN Deficiency

PTEN (phosphatase and tensin homolog) deficiency is present in approximately one in four (25%) patients with mAPMN/S prostate cancer. The loss of PTEN leads to hyperactivation of the PI3K/AKT cell-signaling pathway, driving rapid, aggressive tumor growth and resistance to standard hormonal therapies.¹ PTEN deficiency is an independent risk factor for poor prognosis.

Concurrently with this approval, the FDA approved a companion immunohistochemistry (IHC) diagnostic test to identify PTEN-deficient tumors at the time of diagnosis², emphasizing the growing role of biomarker-driven personalized medicine in prostate cancer.

Verbatim Quotes

• Daniel George, MD, Director of Genitourinary Oncology at Duke Cancer Institute:

“Patients with PTEN-deficient metastatic hormone-sensitive prostate cancer, now called metastatic androgen pathway modulation-naïve or 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 with the potential to improve their lives and change the course of disease.”

• Dave Fredrickson, Executive Vice President, Oncology Business Unit at AstraZeneca:

“CAPItello-281 showed that for the first time, we can target a key driver of this disease to bring meaningful benefit to the one in four patients with this form of prostate cancer who urgently need biomarker-directed therapies. Today’s approval makes clear the importance of testing for actionable biomarkers, including PTEN deficiency, in prostate cancer.”