Niraparib/DAT Abiraterone Receives EU Approval in Prostate Cancer Subtype

The European Commission has granted approval to niraparib (Zejula) in combination with dual action abiraterone acetate tablets for treating patients with metastatic castration-resistant prostate cancer (mCRPC) harboring a germline and/or somatic BRCA1/2 mutation, according to a press release from Janssen Pharmaceutical Companies.¹

Previously, investigators submitted a NDA for niraparib plus dual action abiraterone acetate tablets and prednisone as treatment for BRCA-positive metastatic castration-resistant prostate cancer.

Supporting data for the European Commission’s approval of the regimen came from the phase 3 MAGNITUDE study (NCT03748641). In the study, niraparib plus abiraterone improved radiographic progression-free survival (rPFS) in all homologous recombination repair (HRR)–positive patients (Hazard ratio, 0.73; 95% CI, 0.56-0.96; P = .022). With a median follow-up of 24.8 months in a subgroup of patients with BRCA1/2 mutations, the median rPFS was 19.5 months in the niraparib plus abiraterone arm vs 10.9 months in the placebo plus abiraterone arm.

Investigators also identified a trend towards improved overall survival (OS), improved time to symptomatic progression, and clinically meaningful improvement in time-to-initiation of cytotoxic chemotherapy in the niraparib plus abiraterone arm.

Of those with HRR gene alterations, 67% developed grade 3/4 adverse effects (AEs) after receiving niraparib plus abiraterone vs 46.4% of those who received placebo plus abiraterone. The most common grade 3 AEs in each respective arm included anemia (28.3% vs 7.6%) and hypertension (14.6% vs 12.3%). Overall, the observed safety profile of niraparib and abiraterone was consistent with the known profiles of each agent.

“The MAGNITUDE trial was prospectively designed as a precision medicine study to identify the specific population of patients who would most benefit from niraparib with abiraterone acetate plus prednisone, and potentially increase the likelihood of treatment success,” Martin Voegel, EMEA Therapeutic Area Lead Oncology at Janssen-Cilag GmbH, said in the press release. “The results, on which this European Commission approval is based, reinforce the benefit of this niraparib-based combination in effectively addressing BRCA mutations and changing the outlook for patients with mCRPC.”

Investigators of the randomized, double-blind phase 3 MAGNITUDE trial assessed the addition of niraparib to abiraterone in patients with untreated mCRPC with or without HRR alterations. The trial included a total of 423 patients with HRR gene alterations, 53.2% of whom had BRCA mutations. Patients were randomly assigned 1:1 to receive 200 mg of niraparib once daily or matched placebo plus abiraterone dual action tablets.

The primary end point of the trial was rPFS as determined by blinded central independent review. Secondary end points included OS, time-to-initiation of cytotoxic chemotherapy, and time to symptomatic progression.

Patients 18 years and older who had a HRR gene alteration and metastatic disease as documented with CT or MRI were eligible for enrollment on the trial. Additional inclusion criteria included having a score of 3 or lower on the brief pain inventory-short form question number 3 assessing worst pain in the last 24 hours.

Investigators previously submitted a new drug application (NDA) to the FDA seeking approval for niraparib plus abiraterone and prednisone for treating patients with BRCA-positive mCRPC in March 2023.² The NDA was supported by findings from the phase 3 MAGNITUDE trial.

References

1. Janssen marks first approval worldwide for AKEEGA® (niraparib and abiraterone acetate dual action tablet) with EC authorisation for the treatment of patients with metastatic castration resistant prostate cancer with BRCA1/2 mutations. News release. Janssen Pharmaceutical Companies. April 21, 2023. Accessed April 24, 2023. bit.ly/41RaZzd
2. 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 April 24, 2023. http://bit.ly/3kFMqFy