FDA Approves Akeega Combo in BRCA2+ Metastatic Prostate Cancer

The U.S. Food and Drug Administration (FDA) has approved niraparib (Zejula) plus Akeega (abiraterone acetate) and prednisone (APP) for adults with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC), as determined by an FDA-approved test, according to a news release from the regulatory agency.

The phase 3 AMPLITUDE trial evaluated the now-FDA-approved treatment combination. The randomized, double-blind trial evaluated 696 patients with homologous recombination repair (HRR) gene-mutated mCSPC, demonstrating a statistically significant improvement in radiographic progression-free survival (rPFS) for patients treated with Akeega combination therapy compared with placebo plus APP.

Moreover, in an exploratory analysis of 323 patients with BRCA2-mutated disease, the median rPFS was not estimable for those treated with the Akeega combination therapy compared with 26 months for placebo therapy. Additionally, another analysis observed 373 patients with non-BRCA2–mutated disease and data suggested that the overall benefit was mainly driven by patients with BRCA2-mutated.

At the first interim analysis for overall survival, 91 deaths occurred in patients with BRCA2 mutations, including 36 (22%) receiving Akeega and 55 (34%) receiving placebo plus APP.

The recommended dose of Akeega is 200 milligrams (mg) of Zejula and 1,000 mg of APP orally once daily with 5 mg prednisone, also given once daily, continued until disease progression or unacceptable side effects. Patients should also receive a gonadotropin-releasing hormone analog or have had a bilateral orchiectomy.

The prescribing information for Akeega includes warnings for myelodysplastic syndrome and acute myeloid leukemia, myelosuppression, low potassium, fluid retention and heart-related side effects, liver toxicity, adrenal insufficiency, low blood sugar, increased fractures and death with radium Ra 223 dichloride, posterior reversible encephalopathy syndrome, and embryo-fetal toxicity.

Health-Related Quality of Life Study Findings for Akeega

Among patients with prostate cancer with HRR mutations receiving Akeega plus prednisone, health-related quality of life remained near baseline, according to patient-reported outcomes from the AMPLITUDE trial, presented at the 2025 ESMO Congress.

In this presentation of data, investigations shared that the 696 patients observed were randomly assigned to Akeega or placebo plus APP, with 94% completing questionnaires at screening, during cycles one through 25, and every four months until the end of treatment. Questionnaires included FACT-P, EQ-5D-5L, and BPI-SF.

Between 76% and 85% of patients receiving Akeega reported being “not at all” or “a little bit” bothered by side effects versus 86% to 93% reporting on the same question in the placebo arm. FACT-G scores showed minimal differences.

Early decreases in Akeega scores during cycles two to four, attributed to hypertension and anemia, returned to baseline from cycle five onward. Scores declined slightly toward the end of the trial, likely reflecting more patients remaining on study in later cycles.

FACT-P scores followed a similar pattern, with mean baseline scores of 113.3 for Akeega and 112.7 for placebo and minimal overall changes. Physical well-being subscale and EQ-5D-5L scores showed small fluctuations but remained comparable between arms. Time to worsening pain intensity measured by BPI-SF was also similar.

The AMPLITUDE study met its primary end point of rPFS and showed a 37% reduction in risk, along with a 50% reduction in time to symptomatic progression. Median follow-up was 30.8 months, with a median of 25 cycles in both arms. Both arms also received androgen deprivation therapy, the current standard of care for this patient population, with or without an androgen receptor inhibitor or docetaxel.

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