The Oncologic Drugs Advisory Committee (ODAC) voted 7 to 1, with one abstention, that the regimen demonstrated a favorable benefit-risk profile for AstraZeneca’s TRUQAP (capivasertib) in combination with abiraterone and androgen deprivation therapy (ADT) for patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC). The recommendation, based on results from the phase 3 CAPItello-281 trial, highlights a potential new targeted approach in a high-risk population with limited options. Although not binding, ODAC recommendations often carry significant weight in shaping decisions by the U.S. Food and Drug Administration.

Background

Metastatic hormone-sensitive prostate cancer remains a challenging disease, particularly among patients with PTEN-deficient tumors, which are associated with aggressive biology and poorer clinical outcomes. While androgen deprivation therapy combined with androgen receptor pathway inhibitors such as abiraterone has improved outcomes, resistance remains inevitable for many patients.

PTEN loss, present in approximately one in four patients with mHSPC, drives activation of the PI3K/AKT pathway and has been associated with treatment resistance and disease progression. This has created a strong rationale for incorporating targeted therapies aimed at improving disease control in this subgroup.

ODAC Review and Vote

During the advisory committee meeting, members evaluated whether the addition of capivasertib to standard-of-care therapy demonstrated a meaningful clinical benefit in the patient population. The panel ultimately voted in favor of the regimen, reflecting confidence that the observed efficacy outweighed safety concerns in this setting.

Discussion centered on the magnitude and clinical relevance of progression delay, as well as the unmet need in PTEN-deficient disease. While some uncertainty remained, particularly given immature overall survival data, the committee acknowledged that delaying disease progression represents a meaningful endpoint in a population with historically limited targeted treatment options.

Clinical Data Supporting the Decision

The ODAC decision was supported by findings from the CAPItello-281 phase 3 trial, which evaluated capivasertib in combination with abiraterone and ADT in patients with PTEN-deficient de novo mHSPC.

The study demonstrated a statistically significant 19% reduction in the risk of radiographic progression or death compared with abiraterone and ADT alone (HR 0.81; P=0.034), with a median radiographic progression-free survival of 33.2 months versus 25.7 months in the control arm.

Additional benefits were observed across key secondary endpoints, including delayed time to castration resistance and favorable trends in prostate-specific antigen progression and symptomatic skeletal event–free survival.

The magnitude of rPFS improvement, while modest, is notable given the aggressive nature of PTEN-deficient disease, a subgroup historically characterized by resistance to standard hormonal therapies. These findings were presented at the European Society for Medical Oncology Congress and published in Annals of Oncology.

Safety Considerations

The safety profile of capivasertib in combination with abiraterone and ADT was consistent with known toxicities of the regimen, though the addition of a targeted therapy was associated with a higher incidence of Grade 3 or higher adverse events.

Grade 3 or higher adverse events occurred in 67% of patients receiving the combination compared with 40.4% in the control arm. Common toxicities included rash, hyperglycemia, hypokalemia, diarrhea, hypertension, and anemia.

Despite the increased toxicity burden, these adverse events were considered manageable with appropriate monitoring and dose modifications, contributing to the committee’s favorable benefit-risk assessment.

Clinical Implications

The favorable ODAC vote signals a potential shift toward biomarker-driven treatment strategies in metastatic hormone-sensitive prostate cancer. If approved, capivasertib would represent a potential targeted treatment option for PTEN-deficient disease in this setting.

In clinical practice, integration of this regimen will likely depend on routine PTEN testing, patient selection, and clinician familiarity with managing associated metabolic and dermatologic toxicities. The combination may be particularly relevant for patients with high-risk disease features where delaying progression is a key treatment priority.

These findings are also likely to generate discussion at upcoming meetings such as the American Society of Clinical Oncology Annual Meeting, particularly regarding the role of biomarker-driven intensification strategies in the hormone-sensitive setting.

Bottom Line

The ODAC’s 7–1 vote in favor of capivasertib plus abiraterone and ADT underscores the growing importance of targeted approaches in prostate cancer. Supported by CAPItello-281 data, the regimen offers a promising option for patients with PTEN-deficient mHSPC, though longer-term outcomes and real-world experience will be critical in defining its role. The oncology community now awaits the FDA’s final decision.

Sources:

AstraZeneca. (2026). TRUQAP (capivasertib) recommended by FDA Advisory Committee for PTEN-deficient metastatic hormone-sensitive prostate cancer. Retrieved from https://www.astrazeneca-us.com/media/press-releases/2026/TRUQAP-capivasertib-recommended-by-FDA-Advisory-Committee-for-PTEN-deficient-metastatic-hormone-sensitive-prostate-cancer.html

Fizazi, K., Clarke, N. W., De Santis, M., et al. (2026). Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study. Annals of Oncology, 37(1), 53–68. https://doi.org/10.1016/j.annonc.2025.10.004