AstraZeneca’s Truqap (capivasertib) has been approved in the US 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, previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC). The regimen is indicated for patients whose tumors are confirmed as PTEN-deficient using an FDA-authorized test. The decision marks the first approval of an AKT inhibitor in this aggressive prostate cancer subset and moves the first-in-class agent into its second tumor type.
The approval is supported by data showing that the Truqap combination reduced the risk of radiographic disease progression or death by 19% compared with abiraterone and androgen deprivation therapy (ADT) plus placebo. Median radiographic progression-free survival was 33.2 months with Truqap plus abiraterone and ADT versus 25.7 months with abiraterone and ADT alone, a 7.5-month improvement. Overall survival data were immature at the time of the primary analysis but numerically favored the Truqap combination, and follow-up is ongoing to further assess this key secondary endpoint.
Prostate cancer is the second most common cancer in men and the fifth leading cause of male cancer death globally, with more than 1.4 million new cases each year. An estimated 200,000 patients worldwide, including about 35,000 in the US, are diagnosed annually with mAPMN/S prostate cancer, and roughly one in four of these patients has PTEN-deficient tumors, which drive cancer growth and are associated with worse outcomes. PTEN deficiency is an independent risk factor and can be identified by immunohistochemistry at diagnosis, making biomarker testing central to identifying candidates for the Truqap combination.
Investigators noted that patients with PTEN-deficient mAPMN/S prostate cancer experience faster disease progression and poorer prognosis than those without PTEN deficiency, making prolonged remission and delay of progression a high priority. AstraZeneca executives said the approval demonstrates that targeting a key driver of disease can deliver meaningful clinical benefit to this biomarker-defined subgroup and underscores the importance of routine testing for actionable biomarkers, including PTEN deficiency, in prostate cancer.
The safety profile of Truqap in combination with abiraterone and ADT was broadly consistent with the known profiles of the individual agents. Grade 3 or higher adverse events occurred in 67% of patients receiving the Truqap combination, with rash (12.3%) and hyperglycemia (10.3%) reported as the most common severe events. Alongside the drug approval, the FDA cleared a companion diagnostic to detect PTEN deficiency in prostate adenocarcinoma. A regulatory application for the Truqap combination in this setting is currently under review in the European Union.
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