FDA Approves Capivasertib Plus Abiraterone in PTEN-Deficient Metastatic Prostate Cancer: CAPItello-281 Phase 3 Data

KEY FINDINGS

• Approval: On 12 June 2026 the FDA approved capivasertib (Truqap) plus abiraterone acetate and prednisone for PTEN-deficient mAPMN/S - the first and only targeted therapy approved for this patient subgroup defined by PTEN loss.
• CAPItello-281 phase 3: Median rPFS was 33.2 months in the capivasertib arm versus 25.7 months (placebo) - HR 0.81 (95% CI 0.66-0.98; p=0.034), an approximately 19% risk reduction.
• Companion diagnostic: The VENTANA PTEN (SP218) RxDx Assay received FDA approval as an immunohistochemical method.
• Frequency: PTEN loss is seen in approximately 20-25% of patients with metastatic prostate cancer and is associated with a poor prognosis.

Background: PTEN Loss and the PI3K/AKT Pathway

PTEN (Phosphatase and Tensin Homolog) is a tumour suppressor gene. PTEN loss is detected in approximately 20-25% of patients with metastatic prostate cancer. This loss leads to activation of the PI3K/AKT signalling pathway and is associated with accelerated tumour progression, resistance to androgen pathway therapy and a worse prognosis.

Capivasertib (Truqap) is a potent and selective AKT inhibitor; it inhibits the AKT1, AKT2 and AKT3 isoforms and thereby suppresses the PI3K/AKT/mTOR signalling pathway. Because this pathway is hyperactive in tumours with PTEN loss, capivasertib offers a particularly effective treatment strategy in these patients.

Abiraterone acetate, in turn, suppresses androgen biosynthesis as a CYP17A1 inhibitor. The combination of capivasertib with abiraterone aims to prevent cross-resistance by simultaneously targeting the androgen pathway and the PI3K/AKT pathway.

Study Design

CAPItello-281 (NCT04493853) is an international, randomized, double-blind, placebo-controlled phase 3 trial conducted in patients with PTEN-deficient metastatic androgen pathway modulation-naive or sensitive prostate cancer (previously termed mHSPC).

Key Results

The trial met its primary endpoint of rPFS, showing that capivasertib plus abiraterone provided a significant advantage over placebo plus abiraterone.

* OS data were not yet mature at the time of reporting.

Safety Profile

Recommended dosing: capivasertib (Truqap) 400 mg orally twice daily (approximately 12 hours apart) on a 4 days on / 3 days off cycle, until disease progression or unacceptable toxicity. Abiraterone acetate 1,000 mg orally once daily; prednisone 5 mg orally once daily. Concurrent use of a GnRH analogue or prior bilateral orchiectomy is required in patients receiving capivasertib plus abiraterone.

Implications for Clinical Practice

This approval marks an important turning point in urology and uro-oncology practice in that it brings a molecular stratification approach into the management of mHSPC/mAPMN/S.

1. Routine PTEN testing

Routine assessment of PTEN status in all patients diagnosed with mHSPC now directly influences the treatment decision.

2. Adverse effect management

Patient education and close follow-up should be planned for the proactive management of frequent adverse effects such as diarrhoea, hyperglycaemia and rash.

Conclusion

The FDA approval of capivasertib plus abiraterone and prednisone signals a new era in the management of metastatic prostate cancer. Treatment personalisation based on molecular biomarkers such as PTEN loss is now a clinical reality. Although CAPItello-281 achieved a statistically significant improvement in rPFS, maturation of the OS data is awaited.

Because capivasertib adds toxicity to the existing standard of care (particularly diarrhoea and hyperglycaemia), patient selection and adverse effect management are critically important. Integration into clinical practice requires strengthening PTEN testing infrastructure and a multidisciplinary approach.

References

• FDA approves capivasertib plus abiraterone and prednisone for PTEN-deficient mHSPC. Urology Times. 12 June 2026. - urologytimes.com
• FDA approves capivasertib with abiraterone and prednisone for PTEN-deficient androgen pathway modulation-naive or -sensitive prostate cancer. U.S. Food and Drug Administration. - fda.gov
• Fizazi K, Clarke NW, Santis MD, et al. Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study. Ann Oncol. 2026;37(1):53-68. doi:10.1016/j.annonc.2025.10.004
• TRUQAP (capivasertib) combination approved in the US as first and only targeted treatment for PTEN-deficient metastatic hormone-sensitive prostate cancer. Prostate Cancer Foundation. - pcf.org
• FDA Approves Capivasertib Plus Abiraterone and Prednisone for PTEN-Deficient mHSPC. OncLive. - onclive.com