Capivasertib Combo Earns FDA Approval in PTEN-Deficient Metastatic HSPC

The FDA has approved the combination of capivasertib (Truqap) plus abiraterone (Zytiga) and predinsone as a treatment for patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (HSPC), according to a news release from the developer, AstraZeneca.¹

Support for the approval came from the phase 3 CAPItello-281 trial (NCT04493853), which evaluated the combination in the aforementioned patient group. Findings previously presented at the European Society of Medical Oncology (ESMO) 2025 Congress and published in the Annals of Oncology revealed a significant improvement in the primary end point of radiographic progression-free survival (rPFS).² The investigational regimen elicited a median rPFS of 33.2 months vs 25.7 months with placebo plus abiraterone (HR, 0.81; 95% CI, 0.66-0.98; P <.034).

Moreover, for the key secondary end point of overall survival (OS), at a maturity of 26.4%, the HR for OS numerically favored the capivasertib-based regimen but did not reach significance (HR, 0.90; 95% CI, 0.71-1.15; P = 0.401).

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 98.8% vs 92.0% of the respective arms, 67.0% vs 40.4% of whom experienced grade 3 or higher events. The most common AEs included diarrhea (51.9% vs 8.0%), hyperglycemia (38.0% vs 12.9%), and rash (35.4% vs 7.0%).

Serious AEs were reported in 42.5% of the capivasertib arm vs 26.0% of the placebo arm. A total of 16.2% vs 20.2% of patients in each arm died due to disease progression, with a further 7.2% vs 5.2% having died due to AEs. Of those, 1.2% vs 0.2% of patients experienced AE-related deaths deemed related to treatment with capivasertib or placebo, respectively.

“Patients with PTEN-deficient metastatic [HSPC], now called metastatic androgen pathway modulation-naive or sensitive prostate cancer, experience faster progression and worse prognosis than those without PTEN deficiency,” Daniel George, MD, director of Genitourinary Oncology at Duke Cancer Institute and investigator for the CAPItello-281 trial, stated in the release.¹ “Keeping patients with this form of prostate cancer in remission and free from disease progression as long as possible is a high priority. Today’s landmark approval of the capivasertib combination as the first and only targeted treatment option for these patients represents a significant clinical advance with the potential to improve their lives and change the course of disease.”

Concurrent with this approval, the FDA has also approved a companion diagnostic to detect PTEN deficiency in prostate adenocarcinoma tumors.

References

1. Truqap combination approved in the US as first and only targeted treatment for PTEN-deficient metastatic hormone-sensitive prostate cancer. News release. AstraZeneca. June 12, 2026. Accessed June 12, 2026. https://tinyurl.com/3mwyj5aj
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. 2026;37(1):P53-68. doi: 10.1016/j.annonc.2025.10.004