The U.S. Food and Drug Administration (FDA) has approved capivasertib (Truqap) in combination with abiraterone and prednisone for the treatment of PTEN-deficient metastatic androgen pathway modulation-naive or sensitive (mAPMN/S) prostate cancer (also referred to as metastatic hormone-sensitive prostate cancer [mHSPC]), as detected by an FDA-authorized test. Capivasertib is a novel pyrrolopyrimidine-derived agent, and it is a strong and selective inhibitor of AKT1, AKT2, and AKT3. PTEN loss activates the PI3K/AKT pathway, making AKT inhibition with capivasertib a rational therapeutic approach in PTEN-deficient mAPMN/S. This is the first targeted treatment for this indication.
The FDA also approved the Ventana PTEN (SP218) RxDx Assay as a companion diagnostic device to identify patients with PTEN-deficient prostate cancer for treatment with capivasertib.
The approval of the novel combination and companion diagnostic test was announced on June 12, 2026.
Standard treatment for patients with mHSPC is abiraterone, which is an androgen receptor pathway inhibitor (ARPI), in combination with prednisone/prednisolone and androgen deprivation therapy (ADT).
One in four of these patients have PTEN-deficient tumors, an aggressive form of the disease associated with poor outcomes. PTEN deficiency is an independent risk factor regardless of other clinical characteristics, and can be identified by immunohistochemistry testing at time of diagnosis.
CAPItello-281
The FDA approval of this novel combination was based on the results of the phase III CAPItello-281 trial, which showed a statistically significant 19% reduction in the risk of radiographic disease progression or death and a clinically meaningful improvement in median radiographic progression–free survival of 7.5 months with capivasertib in combination with abiraterone and ADT vs a control arm receiving treatment with abiraterone and ADT with placebo (based on a hazard ratio [HR] of 0.81; 95% confidence interval [CI] = 0.66–0.98; P = .034).1,2 Median radiographic progression–free survival was 33.2 months for the capivasertib arm vs 25.7 months for the comparator arm. Whereas overall survival data were immature at the time of the primary analysis, results numerically favored the capivasertib combination vs the comparator arm. The trial will continue as planned to further assess overall survival as a key seconary endpoint.
The safety profile of capivasertib in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each therapy. Grade 3 or higher adverse events occurred in 67% of patients treated with the capivasertib combination, with rash (12.3%) and hyperglycemia (10.3%) being the most frequently reported.
REFERENCES
1. George DJ, Clarke NW, De Santis M, et al: CAPItello-281. 2026 ASCO GU Cancers Symposium. Abstract 14. Presented February 26, 2026.
2. Fizazi K, Clarke NW, De Santis M, et al: Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study. Ann Oncol 37:53-68, 2026.
