On December 12, the U.S. Food and Drug Administration (FDA) approved the PARP inhibitor niraparib and the hormone therapy abiraterone acetate (Akeega) with prednisone for adults with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer, as determined by an FDA-approved test.
AMPLITUDE
Efficacy was evaluated in AMPLITUDE (ClinicalTrials.gov identifier NCT04497844), a randomized, double-blind trial in 696 patients with homologous recombination repair (HRR) gene–mutated metastatic castration-sensitive prostate cancer. Patients were randomly assigned 1:1 to receive niraparib and abiraterone acetate plus prednisone (AAP) or placebo and AAP. All patients also received continued androgen-deprivation therapy.
The major efficacy outcome measure was investigator-assessed radiographic progression–free survival; overall survival was an additional efficacy outcome.
The trial demonstrated a statistically significant improvement in radiographic progression–free survival for niraparib and AAP compared to placebo and AAP in the overall population of patients with HRR-mutated disease. In an exploratory analysis of 323 patients with BRCA2-mutated metastatic castration-sensitive prostate cancer, the hazard ratio (HR) for radiographic progression–free survival was 0.46 (95% confidence interval [CI] = 0.32–0.66), with median radiographic progression–free survival being not estimable (95% CI = 41 months–not estimable) for niraparib and AAP and 26 months (95% CI = 18–28 months) for placebo and AAP. In an exploratory analysis in 373 patients with non–BRCA2-mutated disease, the HR for radiographic progression–free survival was 0.88 (95% CI = 0.63–1.24), indicating that the overall improvement was primarily attributed to the results seen in patients with BRCA2-mutated disease.
At the first interim analysis for overall survival, 91 deaths had occurred in the BRCA2-mutated population, including 36 (22%) on the niraparib and AAP arm and 55 (34%) on the placebo and AAP arm.
The prescribing information for niraparib and AAP includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia; myelosuppression; hypokalemia; fluid retention and cardiovascular adverse reactions; hepatoxicity; adrenocortical insufficiency; hypoglycemia; increased fractures and mortality in combination with radium Ra 223 dichloride; posterior reversible encephalopathy syndrome; and embryo-fetal toxicity.
The recommended dose is 200 mg niraparib and 1,000 mg abiraterone acetate orally once daily in combination with 5 mg prednisone once daily until disease progression or unacceptable toxicity. Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review.
