FDA advisory committee backs AstraZeneca’s Truqap combination for PTEN-deficient metastatic hormone-sensitive prostate cancer

The FDA’s Oncologic Drugs Advisory Committee has voted 7 to 1 in favour of a favourable benefit-risk profile for AstraZeneca’s Truqap (capivasertib) in combination with abiraterone and androgen deprivation therapy for patients with PTEN-deficient metastatic hormone-sensitive prostate cancer. The vote represents a significant step toward what would be the first and only targeted treatment combination to demonstrate benefit in this specific subtype of prostate cancer.

PTEN-deficient metastatic hormone-sensitive prostate cancer is an aggressive form of the disease affecting approximately one in four patients with this stage of prostate cancer. It is associated with poor outcomes, rapid progression to more advanced and lethal stages, and until now, very limited treatment options.

The committee’s recommendation is based on results from the CAPItello-281 Phase III trial, which showed a statistically significant 19% reduction in the risk of radiographic disease progression or death with the Truqap combination versus abiraterone and ADT with placebo. Median radiographic progression-free survival was 33.2 months with the Truqap combination compared to 25.7 months in the comparator arm, a clinically meaningful improvement of 7.5 months. Consistent benefits were also observed across key secondary endpoints including time to castration resistance, PSA progression and symptomatic skeletal event-free survival. Overall survival data remain immature but numerically favour the Truqap combination at the most recent interim analysis.

Daniel George, Director of Genitourinary Oncology at Duke Cancer Institute and a trial investigator, welcomed the outcome for a patient population with few options: “Patients identified to have PTEN-deficient metastatic hormone-sensitive prostate cancer have an aggressive form of the disease and currently experience poor outcomes. Their disease significantly impacts their quality of life and inevitably progresses to more advanced stages that are associated with high mortality rates. Today’s recommendation of the capivasertib combination is welcome news for both patients and clinicians to address an urgent need for new treatments that delay progression.”

Susan Galbraith, AstraZeneca’s Executive Vice President for Oncology Haematology R&D, highlighted the broader significance of how the trial was designed: “CAPItello-281 is the first pivotal trial to prospectively define PTEN-deficient metastatic hormone-sensitive prostate cancer and its severe course of disease. The Committee’s recognition of the unmet need in patients with PTEN-deficiency and of the benefit seen with the Truqap combination verifies its potential to address this significant need and optimise outcomes for patients.”

On the safety side, Grade 3 or higher adverse events occurred in 67% of patients in the Truqap arm versus 40.4% in the comparator arm, consistent with the addition of a targeted therapy to background treatment. The most common higher-grade events included rash, hyperglycaemia, hypokalaemia, diarrhoea, hypertension and anaemia.

The FDA is not bound by the advisory committee’s recommendation but will take it into consideration as it continues its review. A regulatory application for the same indication is also under review in the EU.

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Related Topics and Keywords

AstraZeneca's Truqap, prostate cancer, PTEN-deficient metastatic hormone-sensitive prostate cancer