FDA Approves FoundationOne CDx as a Companion Diagnostic for Niraparib Plus Abiraterone Acetate in BRCA+ mCRPC


FoundationOne CDx is a next-generation sequencing–based in vitro diagnostic device developed to detect substitutions, insertion, and deletion alterations using 1 tissue sample.

FDA Approves FoundationOne CDx as a Companion Diagnostic for Niraparib Plus Abiraterone Acetate in BRCA+ mCRPC

FDA Approves FoundationOne CDx as a Companion Diagnostic for Niraparib Plus Abiraterone Acetate in BRCA+ mCRPC

The FDA has approved the companion diagnostic, FoundationOne CDx, to help identify patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) who are eligible for the tablet (Akeega), which consists of niraparib (Zejula) plus abiraterone acetate (Zytiga) which was recently approved for use in combination with prednisone for this population.

The next-generation sequencing–based in vitro diagnostic device was developed to detect substitutions, insertion, and deletion alterations, as well as copy number alterations in 324 genes and select gene rearrangements, using 1 tissue sample. The test is also able to identify genomic signatures such as microsatellite instability and tumor mutational burden.

“With such a rapidly evolving therapeutic landscape in prostate cancer, high-quality companion diagnostics are important tools to support oncologists in the development of personalized treatment plans for each unique patient,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated in a press release. “This companion diagnostic specifically will help enable broader access to an important new therapy option in BRCA1/2-positive mCRPC. We look forward to ongoing collaboration with Janssen to help bring more treatment options to patients facing a cancer diagnosis.”

On August 11, 2023, the FDA approved the fixed-dose combination of niraparib plus abiraterone acetate, paired with prednisone, based on findings from cohort 1 of the phase 3 MAGNITUDE trial (NCT03748641).2,3 In those with BRCA-mutated disease, the combination significantly improved radiographic progression-free survival (rPFS) compared with abiraterone acetate and prednisone alone, at a median of 16.6 months (95% CI, 13.9-not evaluable [NE]) and 10.9 months (95% CI, 8.3-13.8), respectively (HR, 0.53; 95% CI, 0.36-0.79; = .0014).

Data from an exploratory overall survival (OS) analysis conducted in those with BRCA-mutated disease, also favored the tablet arm vs the control arm, with a median of 30.4 months (95% CI, 27.6-NE) vs 28.6 months (95% CI, 23.8-33.0), respectively (HR, 0.79; 95% CI, 0.55-1.12).

Although an rPFS improvement was observed with niraparib plus abiraterone and prednisone vs abiraterone/prednisone alone in the overall cohort 1 intention-to-treat (ITT) population who had homologous recombination repair (HRR) deficiency (HR, 0.73; 95% CI, 0.56-0.96; = .0217), the HR for rPFS was 0.99 (95% CI, 0.67-1.44) in a subset of patients with non-BRCA HRR mutations. The HR for OS was 1.13 (95% CI, 0.77-1.64). This indicates “that the improvement in ITT HRR gene–mutated population was primarily attributed to the results seen in the subgroup of patients with BRCA mutations,” according to the FDA.

The double-blind, placebo-controlled, multicohort, multicenter MAGNITUDE trial enrolled a total of 423 patients with HRR gene–mutated mCRPC who had not previously received systemic treatment in the mCRPC setting except for a short duration of up to 4 months of abiraterone acetate and prednisone and ongoing androgen deprivation therapy.3 Notably, patients were allowed to have previously received docetaxel or androgen receptor (AR)–targeted therapies in the metastatic castration-sensitive disease setting or the nonmetastatic castration-resistant disease setting.

Study participants (n = 423) were randomly assigned 1:1 to receive niraparib at 200 mg plus abiraterone acetate at 100 mg (n = 212) or placebo and abiraterone acetate (n = 211). Treatment continued until disease progression or intolerable toxicity. All participants were given prednisone at a daily dose of 10 mg and a gonadotropin-releasing hormone analog or previous bilateral orchiectomy.

Stratification factors included previous receipt of docetaxel in the castration-sensitive setting (yes vs no), previous AR-targeted therapy for the castration-sensitive or -resistant setting (yes vs no), previous abiraterone acetate for castration-resistant disease (yes vs no), and BRCA mutational status (BRCA mutations vs other). Fifty-three percent of the 423 patients had BRCA-mutated disease; 7% had BRCA1 mutations, 78% had BRCA2 mutations, and 15% had BRCA mutations in combination with other HRR gene mutations.

In the 225 patients with BRCA-mutated disease, the median age was 68 years (range, 43-100); 72% of patients were White. Regarding ECOG performance status, 66% had a status of 0 and 34% had a status of 1. Moreover, 24%, 5%, and 26% of patients previously received docetaxel, an AR-targeted therapy, or abiraterone acetate/prednisone for up to 4 months for castration-resistant disease, respectively. Additionally, 37% of patients had bone-only metastases and 21% had visceral metastases.

rPFS represented the major efficacy outcome measure of the trial, and this was evaluated by blinded independent central review in accordance with RECIST v1.1 and Prostate Cancer Working Group-3 criteria. OS served as an additional measure of interest.

Safety was evaluated in cohort 1 of the trial. The median duration of exposure to the regimen was 18 months, with a range of 0 to 37 months. Dose reductions due to adverse effects (AEs) were needed in 28% of patients, and dose interruptions were required for 50% of patients. Fifteen percent of patients experienced toxicities that resulted in treatment discontinuation.

Forty-one percent of patients had serious AEs, which included COVID-19 (7%), anemia (4.4%), pneumonia (3.5%), and hemorrhage (3.5%). Fatal AEs were experienced by 9% of patients and included COVID-19 (5%), cardiopulmonary arrest (1%), dyspnea (1%), pneumonia (1%), and septic shock (1%).

The most common AEs experienced with the tablet by more than 10% of patients included musculoskeletal pain (all grade, 44%; grade 3 or 4, 4%), fatigue (43%; 5%), constipation (34%; 1%), hypertension (33%; 14%), nausea (33%; 1%), edema (17%; 0%), dyspnea (15%; 1%), reduced appetite (15%; 2%), vomiting (15%; 0%), dizziness (14%; 0%), COVID-19 (13%; 7%), abdominal pain (12%; 2%), hemorrhage (12%; 2%), headache (12%; 1%), urinary tract infection (12%; 3%), cough (12%; 0%), insomnia (12%; 0%), decreased weight (10%; 1%), arrhythmia (10%; 2%), fall (10%; 1%), and pyrexia (10%; 2%).

BRCA1- or BRCA2-mutated metastatic castration-resistant prostate cancer has had a devastating impact on so many men and their families,” Shelby Moneer, vice president of Patient Programs and Education at ZERO Prostate Cancer, added in the press release.1 “We are so encouraged to see continued progress in advancing treatment options and diagnostics for this devastating condition.”


  1. US Food and Drug Administration (FDA) approves FoundationOne CDx as a companion diagnostic for Janssen’s Akeega (niraparib and abiraterone acetate dual action tablet) for patients with BRCA-positive metastatic castration-resistant prostate cancer. News release. Foundation Medicine. August 14, 2023. Accessed August 14, 2023. https://www.foundationmedicine.com/press-releases/77d12149-fab5-443c-8e7a-1b46085bb1c2
  2. US FDA approves Akeega (niraparib and abiraterone acetate), the first-and-only dual action tablet for the treatment of patients with BRCA-positive metastatic castration-resistant prostate cancer. News release. Janssen. August 11, 2023. Accessed August 11, 2023. https://www.prnewswire.com/news-releases/us-fda-approves-akeega-niraparib-and-abiraterone-acetate-the-first-and-only-dual-action-tablet-for-the-treatment-of-patients-with-brca-positive-metastatic-castration-resistant-prostate-cancer-301899028.html
  3. Niraparib plus abiraterone acetate (Akeega) Prescribing Information. Janssen Biotech, Inc.; August 2023. Accessed August 14, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216793s000lbl.pdf
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