FDA approves companion diagnostic for niraparib/abiraterone in BRCA+ mCRPC

The FDA has approved FoundationOne CDx for use as a companion diagnostic to identify patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors harbor BRCA1/2 mutations, making the patient eligible for the combination regimen of niraparib (Zejula) plus abiraterone acetate (Zytiga).¹

“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, ZERO Prostate Cancer, stated in a press release. “We are so encouraged to see continued progress in advancing treatment options and diagnostics for this devastating condition.”

According to Foundation Medicine, the developer of the diagnostic, FoundationOne CDx is a “next-generation sequencing based in vitro diagnostic device” that searchers for genomic alterations in over 300 genes in a tumor tissue sample.¹

Earlier this month, the FDA approved a dual-action tablet (Akeega) that combines niraparib with abiraterone for use with prednisone for the treatment of adult patients with BRCA mutation–positive mCRPC, as detected by an FDA-approved test.²

“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.¹

“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,” added Levy.¹

Approval of niraparib/abiraterone combo tablet

The approval of the niraparib/abiraterone dual-action tablet was based on findings from the phase 3 MAGNITUDE study, which showed that adding the PARP inhibitor niraparib to the antiandrogen agent abiraterone significantly extended radiographic progression-free survival (rPFS) in patients with mCRPC and homologous recombination repair (HRR) gene alterations, such as BRCA1/2.²

Data presented during the 2022 Genitourinary (GU) Cancers Symposium showed that compared with placebo plus abiraterone, niraparib plus abiraterone led to a 47% reduction in the risk of progression or death in patients with BRCA1/2 mutations and a 27% reduction in the risk of progression or death in all patients with HRR gene alterations.³ The median follow-up time was 18.6 months.

In the BRCA1/2 population, the median rPFS was 16.6 months with niraparib plus abiraterone vs 10.9 months with placebo plus abiraterone (HR, 0.53; 95% CI, 0.36-0.79; P = .0014). The investigator-assessed rPFS was 19.3 months with niraparib/abiraterone and 12.4 months with placebo/abiraterone (HR, 0.50; 95% CI, 0.33-0.75; P = .0006).

Among all patients with HRR gene alterations, the median rPFS was 16.5 months vs 13.7 months, respectively (HR, 0.73; 95% CI, 0.56-0.96; P = .0217). Here, the investigator-assessed rPFS was 19.0 months and 13.9 months, respectively (HR, 0.64; 95% CI, 0.49-0.86; nominal P = .0022).

The MAGNITUDE study enrolled patients with mCRPC who had received no more than 4 months of prior abiraterone and prednisone for mCRPC; had an ECOG performance status of 0 or 1; and had a Brief Pain Inventory-Short Form worst pain score of 3 or less. Eligible patients were screened for HRR alterations in ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, and PALB2.

Based on prescreening results, patients were allocated into the biomarker-positive cohort or the biomarker-negative cohort, which had a planned enrollment of 400 and 600 patients, respectively.

Patients were randomized 1:1 to receive 200 mg of niraparib once daily plus abiraterone or placebo plus abiraterone in each of the cohorts.

Updated MAGNITUDE data with an additional 8 months of follow-up were shared at the 2023 GU Cancers Symposium.⁴

With the additional follow-up, the median radiographic rPFS was 16.7 months in the niraparib group vs 13.7 months in the placebo arm (HR, 0.76; 95% CI, 0.60-0.97; nominal P = .0280). Niraparib also yielded a statistically significant benefit in time to symptomatic progression (TSP) vs placebo, with a hazard ratio of 0.60 (95% CI, 0.42-0.84; P = .0029), as well as in TCC, with a hazard ratio of 0.67 (95% CI, 0.47-0.94; P = .0206).

“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, ZERO Prostate Cancer, stated in a press release.¹ “We are so encouraged to see continued progress in advancing treatment options and diagnostics for this devastating condition.”

References

1. U.S. 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. Published online and accessed August 14, 2023. https://www.foundationmedicine.com/press-releases/77d12149-fab5-443c-8e7a-1b46085bb1c2

2. U.S. 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. Published online and 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. Chi KN, Rathkopf DE, Smith MR, et al. Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2022;40(suppl 6):12. doi:10.1200/JCO.2022.40.6_suppl.012

4. Efstathiou E, Smith MR, Sandhu S, et al. Niraparib with abiraterone acetate and prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis (IA2) of MAGNITUDE. J Clin Oncol. 2023;41(suppl 6):170. doi:10.1200/JCO.2023.41.6_suppl.170