Truqap combination wins US approval as first and only targeted treatment for PTEN-deficient metastatic hormone-sensitive prostate cancer

AstraZeneca’s Truqap used in combination with abiraterone and prednisone, has received US approval as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive prostate cancer, a condition previously known as metastatic hormone-sensitive prostate cancer, identified through an FDA-authorised test.

The approval rests on positive findings from the CAPItello-281 Phase III trial, which were shared at the 2025 European Society for Medical Oncology Congress and published in Annals of Oncology.

Prostate cancer ranks as the second most common cancer among men worldwide and the fifth leading cause of cancer-related death in men globally, with over 1.4 million new diagnoses recorded each year. Of these, roughly 200,000 patients globally, including 35,000 in the US, receive a diagnosis of mAPMN/S prostate cancer annually. Among this group, one in four carries PTEN-deficient tumours, a feature that accelerates cancer cell growth and characterises a more aggressive form of the disease tied to weaker outcomes. PTEN deficiency stands as an independent risk factor irrespective of other clinical traits, and can be detected through immunohistochemistry testing at the point of diagnosis.

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

“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,” said Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca.

The primary analysis of the CAPItello-281 Phase III trial revealed a statistically significant 19% reduction in the likelihood of radiographic disease progression or death, alongside a clinically meaningful gain in median radiographic progression-free survival of 7.5 months for those receiving Truqap alongside abiraterone and androgen deprivation therapy, when set against abiraterone and androgen deprivation therapy combined with placebo. Median progression-free survival reached 33.2 months in the Truqap combination arm, compared to 25.7 months in the comparator group. Although overall survival data remained immature at the point of primary analysis, early trends favoured the Truqap combination numerically over the comparator arm, and the trial will continue as planned to further evaluate overall survival as a key secondary endpoint.

Safety findings for the Truqap, abiraterone, and androgen deprivation therapy combination in CAPItello-281 broadly matched the established profiles of each individual medicine. Grade 3 or higher adverse events occurred in 67% of patients receiving the Truqap combination, with rash (12.3%) and hyperglycaemia (10.3%) emerging as the most commonly reported.

Alongside this approval, the FDA also cleared a companion diagnostic test designed to detect PTEN deficiency in tumours of patients with prostate adenocarcinoma.

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Related Topics and Keywords

prostate cancer, PTEN-deficient metastatic hormone-sensitive prostate cancer, truqap