The FDA has approved capivasertib (Truqap, AstraZeneca) in combination with abiraterone and prednisone for men with phosphatase and tensin homolog (PTEN)-deficient metastatic androgen pathway modulation-naive or sensitive (mAPMN/S) prostate cancer, previously known as metastatic hormone-sensitive prostate cancer. 

The agency also approved the Ventana PTEN (SP218) RxDx immunohistochemistry assay (Roche) to identify PTEN-deficient patients for treatment. 

About a quarter of mAPMN/S prostate cancers are PTEN deficient. PTEN normally acts as a brake on the PI3K/AKT pathway. When PTEN is lost or deficient, the brake is released and the pathway becomes overactive, fueling tumor growth. 

Capivasertib, an AKT inhibitor, was previously approved with fulvestrant for advanced hormone receptor-positive breast cancer. 

The prostate cancer approval was based on AstraZeneca’s CAPItello-281 trial in 1012 men with newly diagnosed disease. To qualify for enrollment, men had to have 90% or more of their cancer cell samples stain negative for PTEN on the Ventana assay. They were then evenly randomized to either capivasertib or placebo on a background of abiraterone, prednisone or prednisolone, and androgen deprivation therapy. 

Radiographic progression-free survival, the primary outcome, was 33.2 months in the capivasertib arm vs 25.7 months with placebo (hazard ratio, 0.81; P = 0.034). Overall survival results were immature at the time of the analysis.

Grade 3 or higher adverse events occurred in 67% of patients treated with capivasertib vs 40.4% on placebo, with rash (12.3%) and hyperglycemia (10.3%) being the most frequently reported in the capivasertib arm.

Deaths associated with adverse events were reported in 7.2% of capivasertib vs 5.2% of placebo patients. Capivasertib labeling warns of hyperglycemia, diarrhea, skin reactions, and embryo-fetal toxicity.

The recommended capivasertib dosage is 400 mg orally twice daily for 4 days followed by 3 days off until disease progression or unacceptable toxicity. Patients treated with capivasertib and abiraterone together should also receive a gonadotropin-releasing hormone analog or have had a bilateral orchiectomy.

The CAPItello-281 trial was funded by AstraZeneca.

M. Alexander Otto is a physician assistant and award-wining journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net