FDA Approves Capivasertib Plus Abiraterone and Prednisone for PTEN-Deficient Prostate Cancer

The FDA has approved capivasertib (Truqap) in combination with abiraterone acetate (Zytiga) and prednisone for adults with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer that is PTEN deficient, as identified by an FDA-authorized test.^1,2

The FDA concurrently cleared the VENTANA PTEN (SP218) RxDx assay as a companion diagnostic to identify eligible patients. The decision, covering disease previously classified as metastatic hormone-sensitive prostate cancer (mHSPC), was based on results from the phase 3 CAPItello-281 trial (NCT04493853).

In CAPItello-281, investigators randomly assigned 1012 patients with newly diagnosed, PTEN-deficient mAPMN/S prostate cancer in a 1:1 ratio to receive capivasertib plus abiraterone (n = 507) or placebo plus abiraterone (n = 505), each combined with prednisone or prednisolone and background androgen deprivation therapy (ADT).

The trial's primary end point, investigator-assessed radiographic progression-free survival (rPFS), favored the capivasertib regimen. Median rPFS reached 33.2 months (95% CI, 25.8-44.2) with capivasertib plus abiraterone versus 25.7 months (95% CI, 22.0-29.9) with placebo plus abiraterone (HR, 0.81; 95% CI, 0.66-0.98; two-sided P = .034). The rPFS benefit was generally consistent across prespecified subgroups, regardless of baseline disease risk or extent of metastatic involvement.

Overall survival data were immature at the time of the rPFS analysis, with results at a 51% information fraction showing a numerical but not statistically significant advantage for the capivasertib combination (HR, 0.90; 95% CI, 0.71-1.15; P = .401). Other secondary measures trended favorably for capivasertib, including time to first subsequent therapy (HR, 0.91; 95% CI, 0.75-1.11) and symptomatic skeletal event-free survival (HR, 0.82; 95% CI, 0.66-1.02). Time to castration resistance (HR, 0.77; 95% CI, 0.63-0.94) and time to prostate-specific antigen progression (HR, 0.73; 95% CI, 0.52-1.01) also favored the experimental arm.

The approval followed a 7-to-1 vote, with 1 abstention, by the FDA's Oncologic Drugs Advisory Committee, which concluded that the benefit of adding capivasertib to abiraterone and prednisone outweighed the risks for this population.³

"Patients with PTEN-deficient metastatic hormone-sensitive prostate cancer, now called metastatic androgen pathway modulation-naïve or sensitive prostate cancer, experience faster progression and worse prognosis than those without PTEN deficiency," Daniel J. George, MD, director of genitourinary oncology at Duke Cancer Institute, stated in a news release.⁴ "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."

Safety Findings

Adding capivasertib to the abiraterone backbone increased overall toxicity relative to placebo. The most common adverse events with the capivasertib regimen were diarrhea (51.9% vs 8.0% with placebo), hyperglycemia (38.0% vs 12.9%), and rash (35.4% vs 7.0%). Grade 3 or higher adverse events occurred in 67% of patients receiving the capivasertib combination, most frequently rash (12.3%) and hyperglycemia (10.3%). Serious adverse events were reported in 42.5% of patients in the capivasertib arm versus 26.0% of those receiving placebo, and adverse event-related deaths occurred in 7.2% and 5.2% of patients, respectively. Prescribing information for the combination carries warnings and precautions for hyperglycemia, diarrhea, cutaneous adverse reactions, and embryo-fetal toxicity.

Trial Design and Patient Population

CAPItello-281 is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 trial that enrolled patients with newly diagnosed mAPMN/S prostate cancer whose tumors were prospectively confirmed as PTEN-deficient through central testing.

All patients in the trial received background ADT, with the control arm receiving abiraterone plus ADT, reflecting current treatment intensification standards for this population. Capivasertib is dosed at 400 mg orally twice daily, approximately 12 hours apart, for 4 days followed by 3 days off, continuing until disease progression or unacceptable toxicity.1 Abiraterone acetate is administered at 1000 mg once daily along with prednisone 5 mg once daily, and patients must also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or have undergone bilateral orchiectomy.

“CAPItello-281 showed that for the first time, we can target a key driver of this disease to bring meaningful benefit to the one in four patients with this form of prostate cancer who urgently need biomarker-directed therapies. Today’s approval makes clear the importance of testing for actionable biomarkers, including PTEN deficiency, in prostate cancer,” Dave Fredrickson, executive vice president, Oncology Haematology Business Unit, AstraZeneca, stated in the news release.

References

1. FDA approves capivasertib with abiraterone and prednisone for PTEN-deficient androgen pathway modulation-naïve or -sensitive prostate cancer. News release. FDA. June 12, 2026. Accessed June 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-abiraterone-and-prednisone-pten-deficient-androgen-pathway-modulation

2. 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

3. FDA ODAC votes for capivasertib in hormone-sensitive prostate cancer. Targeted Oncology. Accessed June 14, 2026. https://www.targetedonc.com/view/fda-odac-votes-for-capivasertib-in-hormone-sensitive-prostate-cancer

4. TRUQAP (capivasertib) 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 14, 2026. https://www.businesswire.com/news/home/20260612633536/en/TRUQAP-capivasertib-combination-approved-in-the-US-as-first-and-only-targeted-treatment-for-PTEN-deficient-metastatic-hormone-sensitive-prostate-cancer