The US FDA approved AstraZeneca’s Truqap (capivasertib) in combination with abiraterone and prednisone for adults with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer whose tumors are PTEN-deficient, marking the first approval of an AKT inhibitor in the hormone-sensitive prostate cancer setting. The decision requires companion diagnostic testing and adds a PI3K/AKT-targeted option to a treatment landscape increasingly shaped by biomarker-selected combination regimens.
The approval requires that PTEN deficiency be confirmed using the VENTANA PTEN (SP218) RxDx Assay (Ventana Medical Systems/Roche Diagnostics), which the FDA simultaneously authorized as a companion diagnostic. PTEN deficiency was defined in the trial as ≥90% of viable malignant cells showing no specific cytoplasmic staining by immunohistochemistry. The recommended capivasertib dose is 400 mg orally twice daily on a 4-days-on/3-days-off schedule, combined with abiraterone acetate 1,000 mg once daily and prednisone 5 mg once daily. Patients must also receive a GnRH analog or have undergone bilateral orchiectomy. Prescribing information carries warnings for hyperglycemia, diarrhea, cutaneous adverse reactions, and embryo-fetal toxicity. The FDA advisory committee had previously recommended the combination in this setting.
Efficacy was demonstrated in the CAPItello-281 trial (NCT04305496), a randomized, double-blind, placebo-controlled, multicenter Phase III study enrolling 1,012 adults with newly diagnosed PTEN-deficient mAPMN/S prostate cancer. The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS). Median rPFS was 33.2 months in the capivasertib arm versus 25.7 months in the placebo-plus-abiraterone arm (hazard ratio 0.81 [95% CI: 0.66, 0.98]; p=0.034). Overall survival data were immature at the time of the rPFS analysis.