FDA Receives NDA for Niraparib/DAT Abiraterone in Prostate Cancer Subtype

Investigators submitted a new drug application to the FDA for niraparib (Zejula) plus dual action abiraterone acetate tablets and prednisone for the treatment of patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC), according to a press release from Janssen Pharmaceutical Companies.¹

“As niraparib and abiraterone improves rPFS, time to symptomatic progression, and time to cytotoxic chemotherapy with a trend towards improvement in [OS] observed, these results continue to support genomic testing in mCRPC, as well as use of niraparib and abiraterone in HRR-positive [patients with] mCRPC, particularly those harboring BRCA gene alterations,” according to an expert from Houston Methodist Oncology Partners.

Should the regimen receive approval from the regulatory organization, it would be the first dual action tablet formulation approved for the treatment of BRCA-positive mCRPC.

The application was supported by data from the phase 3 MAGNITUDE study (NCT03748641), in which investigators evaluated the safety and efficacy of niraparib plus abiraterone for front-line mCRPC with or without homologous recombination repair (HRR) alterations.

“Patients with mCRPC and BRCA mutations face a more aggressive form of prostate cancer and high unmet needs in terms of treatment options. The data supporting this submission reinforce the importance of biomarker testing to identify the subgroups of patients that are most likely to respond to a targeted treatment option,” Peter Lebowitz, MD, PhD, global therapeutic area head of Oncology at Janssen Research & Development, LLC, said in the press release.

In the HRR-altered population, 212 patients received 200 mg of niraparib once daily plus 100 mg of abiraterone tablets once daily and 10 mg of prednisone once daily, and 211 received placebo plus abiraterone and prednisone.

Results from the MAGNITUDE trial presented at the 2023 Genitourinary Cancers Symposium indicated that patients within the BRCA-mutant disease population who were treated with niraparib had a median radiographic progression-free survival (rPFS) of 19.5 months compared with 10.9 months in the placebo arm (HR, 0.55; 95% CI, 0.39-0.78; P = .0007).²

Moreover, the median time to symptomatic progression (TSP) in those with BRCA-mutant disease was not estimable among those treated with niraparib vs 23.6 months in the placebo arm (HR, 0.54; 95% CI, 0.35-0.85; P = .0071).

Presenter and lead author Eleni Efstathiou, MD, PhD, section chief of genitourinary medical oncology at Houston Methodist Oncology Partners, explained that the niraparib/abiraterone combination resulted in a 45% reduction in risk of progression or death in the BRCA-mutant population. The study’s median follow-up was 26.8 months.

Additionally, the experimental combination yielded a 44% reduction in risk of necessary chemotherapy treatment along with a trend towards improved overall survival (OS).

The experimental combination also yielded no new safety findings. Common adverse effects in the niraparib and placebo cohorts, respectively, were anemia (50.0% vs 22.7%), hypertension (33.0% vs 22.3%), and constipation (33.0% vs 15.6%).

“As niraparib and abiraterone improves rPFS, time to symptomatic progression, and time to cytotoxic chemotherapy with a trend towards improvement in [OS] observed, these results continue to support genomic testing in mCRPC, as well as use of niraparib and abiraterone in HRR-positive [patients with] mCRPC, particularly those harboring BRCA gene alterations,” Efstathiou concluded.

Secondary end point data are still being collected, including time-to-initiation of cytotoxic chemotherapy, TSP, and OS.

References

1. Janssen submits new drug application to the U.S. Food and Drug Administration seeking approval of niraparib and abiraterone acetate dual-action tablet, plus prednisone, as a first-line targeted treatment for patients with metastatic castration-resistant prostate cancer with BRCA gene mutations. News release. Janssen Pharmaceutical Companies. March 1, 2023. Accessed March 1, 2023. http://bit.ly/3kFMqFy
2. Efstathiou E, Smith MR, Sandhu S, et al. Niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) 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