FDA Green Lights Companion Diagnostic for Niraparib Plus Abiraterone Acetate in BRCA+ mCRPC

The FDA has approved FoundationOne® Liquid CDx for use as a companion diagnostic for the dual-action tablet (Akeega) of niraparib (Zejula) and abiraterone acetate (Zytiga) in the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) harboring deleterious or suspected deleterious BRCA mutations.¹

“We know how challenging it can be to obtain a tissue sample for testing in advanced cancers such as mCRPC, making liquid biopsy an incredibly important tool in a provider’s toolbox for the development of personalized treatment plans for their patients,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated in a news release. “The approval of our liquid biopsy test, along with the previous approval for our tissue biopsy test, will enable more patients to access this important therapy option. Additionally, with the ability to leverage a liquid-based test and reflex to a tissue-based test if needed, healthcare providers can feel confident they have accurate genomic information at their fingertips to guide treatment decisions for patients.”

FoundationOne Liquid CDx is designed to analyze more than 300 cancer-related genes derived from a liquid blood sample and has previously been indicated as a companion diagnostic in non–small cell lung cancer, prostate cancer, breast cancer, and colorectal cancer. It also has a pan tumor indication specific to detecting NTRK1/2/3 fusions.

In August 2023, the FDA approved niraparib and abiraterone acetate, given with prednisone, for the treatment of adult patients with deleterious or suspected deleterious BRCA-positive mCRPC.²

The regulatory decision was supported by data from cohort 1 of the phase 3 MAGNITUDE trial (NCT03748641), which showed that treatment with niraparib plus abiraterone acetate and prednisone led to a statistically significant improvement in radiographic progression-free survival (rPFS) compared with placebo plus abiraterone acetate and prednisone in patients harboring BRCA mutations (n = 225; HR 0.53; 95% CI, 0.36-0.79; P = .0014). Patients treated with niraparib plus abiraterone acetate experienced a median of rPFS of 16.6 months vs 10.9 months for those treated with placebo plus abiraterone acetate.

Notably, a statistically significant improvement in rPFS was observed in the intention-to-treat population (n = 423) in cohort 1, which was comprised of patients with homologous recombination repair (HRR) gene–mutated mCRPC (HR 0.73; 95% CI 0.56, 0.96; P = .0217). However, in the subgroup of patients with non-BRCA HRR mutations (n = 198), the difference in rPFS did not reach statistical significance (HR, 0.99; 95% CI, 0.67-1.44).

An exploratory analysis showed that patients harboring BRCA mutations achieved a median overall survival (OS) of 30.4 months with niraparib plus abiraterone acetate vs 28.6 months for placebo plus abiraterone acetate (HR 0.79; 95% CI, 0.55-1.12). In the non-BRCA–mutated population, OS data trended in favor of the placebo arm (HR,1.13; 95% CI, 0.77-1.64).

The double-blind, placebo-controlled MAGNITUDE trial enrolled patients at least 18 years of age with metastatic prostate cancer with castrate levels of testosterone no higher than 50 ng/dL. Metastatic disease needed to be documented by a positive bone scan or via metastatic lesions on CT/MRI.³

The study consisted of 3 cohorts. Cohort 1 included patients harboring HRR gene alterations; cohort 2 featured patients without HRR alterations; and cohort 3 included patients who were eligible by HRR status.

The only prior systemic therapy patients were allowed to have received in the mCRPC setting was a short duration of prior abiraterone acetate plus prednisone for up to 4 months and ongoing androgen-deprivation therapy. Prior docetaxel or androgen receptor (AR)–targeted therapies in earlier disease settings were permitted.²

Patients were randomly assigned 1:1 to receive niraparib at 200 mg in combination with abiraterone acetate at 1000 mg and prednisone at 10 mg per day, or placebo plus abiraterone acetate and prednisone. Stratification factors included prior treatment with docetaxel, prior AR-targeted therapy, prior abiraterone acetate plus prednisone, and BRCA status.

The trial’s primary end point was rPFS per RECIST 1.1 criteria. Secondary end points included OS, time to symptomatic progression, time to initiation of cytotoxic chemotherapy, and safety.^2,3

The most common adverse effects reported in at least 20% of patients treated with niraparib plus abiraterone acetate and prednisone included decreased hemoglobin, decreased lymphocytes, decreased white blood cells, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, increased creatinine, increased potassium, decreased potassium, and increased aspartate aminotransferase.²

References

1. U.S. Food and Drug Administration (FDA) approves FoundationOne®Liquid CDx as a companion diagnostic for Akeega (niraparib and abiraterone acetate) for patients with BRCA-positive metastatic castration-fesistant prostate cancer. News release. Foundation Medicine. July 1, 2024. Accessed July 1, 2024. https://www.foundationmedicine.com/press-release/fda-approval-foundationone-liquid-cdx-akeega
2. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA-mutated metastatic castration-resistant prostate cancer. FDA. August 11, 2023. Accessed July 1, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-and-abiraterone-acetate-plus-prednisone-brca-mutated-metastatic-castration
3. A study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for treatment of participants with metastatic prostate cancer (MAGNITUDE). ClinicalTrials.gov. Updated May 24, 2024. Accessed July 1, 2024. https://clinicaltrials.gov/study/NCT03748641