FDA ODAC votes in favor of capivasertib plus abiraterone in PTEN-deficient mHSPC

The FDA Oncologic Drugs Advisory Committee (ODAC) voted 7 to 1, with 1 abstaining, in support of a favorable risk-benefit profile for capivasertib (Truqap) in combination with abiraterone (Zytiga) and prednisone for patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PTEN deficiency.¹

During the session, the committee reviewed efficacy and safety data from the phase 3 CAPItello-281 trial (NCT04493853), which is the basis for a supplemental new drug application (sNDA) seeking approval of the capivasertib regimen in mHSPC. The committee specifically discussed whether:

• “The magnitude of radiographic progression-free survival (rPFS) improvement observed in the CAPItello-281 trial represents a clinically meaningful treatment effect in the mHSPC population in the absence of an effect on [overall survival] (OS).
• The overall benefit-risk of the investigational treatment is favorable.”²

The ODAC committee was tasked with answering the question: Based on the CAPItello-281 results, does the benefit of adding capivasertib to abiraterone and prednisone outweigh the risk for the proposed indication?

Among all panel members, 7 voted yes, 1 voted no, and 1 abstained from voting.

Committee members emphasized that the combination demonstrated a statistically significant improvement in rPFS, with some viewing the magnitude of benefit (on the order of several months) as clinically meaningful, particularly for a biomarker-selected subgroup with PTEN deficiency. Several noted that the therapy is unlikely to be appropriate for all patients but could offer meaningful benefit in a more narrowly defined population, reinforcing the value of expanding treatment options and biomarker-driven care. Those who voted “yes” argued that approving this regimen would give physicians that option.

“For these patients with PTEN deficiency and aggressive disease, we need more options, not less,” said Daniel J. George, MD, FASCO, of Duke Cancer Center, on behalf of the sponsor. “If this is an agent that demonstrates clinical benefit with toxicities that are known—granted not all patients going to be able to tolerate that, but for the majority of patients who can—it is a good option for those patients.”

At the same time, concerns were raised about the modest overall benefit relative to the burden, duration, and management complexity of toxicities, including metabolic effects that may require careful monitoring in real-world settings. Some members questioned whether the benefit met thresholds for clinical meaningfulness, while others expressed uncertainty about how well toxicity management observed in trials would translate outside specialized centers, contributing to dissenting and abstaining votes.

Data on capivasertib plus abiraterone and prednisone

The sNDA for capivasertib plus abiraterone and prednisone is supported by data from the phase 3 CAPItello-281 trial (NCT04493853), which included 1012 patients with PTEN-deficient mHSPC. Participants were randomly assigned 1:1 to receive capivasertib plus abiraterone (n = 507) vs placebo plus abiraterone (n = 505) with concomitant prednisone/prednisolone and androgen deprivation therapy (ADT). Baseline characteristics were well-balanced between both arms.

Overall, the trial met its primary end point of rPFS, with a median rPFS of 33.2 months in the treatment arm vs 25.7 months in the control arm (HR, 0.81; 95% CI, 0.66 to 0.98; P = .034). The rPFS benefit was observed across most prespecified subgroups and irrespective of disease risk and metastatic volume of disease.

Related: Daniel George, MD, on capivasertib plus abiraterone in PTEN-deficient mHSPC

The OS results were immature at the time of report. The data showed a numerical improvement in OS with the capivasertib regimen, although the difference did not achieve statistical significance (HR, 0.90; 95% CI, 0.71 to 1.15; P = .401). The combination demonstrated numerical improvements in other secondary end points such as time to first subsequent therapy (HR, 0.91; 95% CI, 0.75 to 1.11), symptomatic skeletal event-free survival (HR, 0.82; 95% CI, 0.66 to 1.02), time to castration resistance (HR, 0.77; 95% CI, 0.63 to 0.94) and time to prostate-specific antigen progression (HR, 0.73; 95% CI, 0.52 to 1.01).

The most common adverse events (AEs) with the capivasertib regimen were diarrhea (51.9% vs 8.0% with placebo), hyperglycemia (38.0% vs 12.9% with placebo), and rash (35.4% vs 7.0% with placebo). Serious AEs were reported in 42.5% of patients in the capivasertib arm and 26.0% of patients in the placebo arm. Deaths associated with an AE occurred in 7.2% of patients in the treatment arm vs 5.2% of patients in the placebo arm.

The application for capivasertib is currently under review by the FDA as well as in the EU. The FDA will consider the recommendation made by ODAC but is not bound to their decision.

REFERENCES
1. April 30, 2026 Meeting of the Oncologic Drugs Advisory Committee (ODAC). YouTube – US Food & Drug Administration. Accessed April 30, 2026. https://www.youtube.com/live/taCx7enN7hk

2. April 30, 2026 Meeting of the Oncologic Drugs Advisory Committee- PM- Combined FDA and AstraZeneca Briefing Document. US Food & Drug Administration. Accessed April 30, 2026. https://www.fda.gov/media/192158/download

3. 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