Niraparib Plus Abiraterone and Prednisone Elicits OS Benefit in BRCA1/2+ mCRPC

The addition of niraparib (Zejula) to abiraterone acetate (Zytiga) and prednisone (AAP) led to a benefit in overall survival (OS) vs treatment with AAP alone in patients with BRCA1/2-mutated (BRCA+) metastatic castration-resistant prostate cancer (mCRPC), according to data from the phase 3 MAGNITUDE trial (NCT03748641) presented at the 2023 ESMO Congress.^1,2

The OS analysis occurred at a median follow-up of 35.9 months (19.2 additional months from the primary analysis). The analysis focused on patients with BRCA+ status, which included 113 patients who received niraparib plus AAP and 112 patients who received placebo plus AAP.

Data showed a median OS of 30.4 months among patients who received niraparib plus AAP, compared with 28.6 months among those who received placebo plus AAP (HR, 0.788; 95% CI, 0.554-1.120; nominal P = .1828). A pre-planned multivariate analysis of pre-specified prognostic factors, including those numerically off-balance at baseline, corroborated the OS benefit in the experimental arm (HR, 0.663; 95% CI, 0.464-0.947; nominal P = .0237).

Beyond OS, other secondary end points assessed in this final analysis included time to symptomatic progression (TSP), time to cytotoxic chemotherapy (TCC), and safety.³

Treatment with niraparib plus AAP was associated with benefits in both TSP (HR, 0.562; 95% CI, 0.371-0.849; nominal P = .0056) and TCC (HR, 0.598; 95% CI, 0.387-0.924; nominal P = .0192).

The median treatment duration was 20.5 months for those in the experimental arm and 14.4 months for those who received placebo plus AAP. Overall, 53.1% (60/113) of patients in the niraparib plus AAP arm discontinued treatment due to disease progression, compared with 76.8% (86/112) of patients in the placebo plus AAP arm.

There were no new safety signals that emerged from the longer follow-up. Adverse events were manageable in both arms, with differences driven by known hematologic toxicities associated with niraparib.

Previous findings from the primary analysis of the MAGNITUDE study showed an improvement in radiographic progression-free survival, the primary end point, with the combination of niraparib plus AAP compared with placebo/AAP in patients with BRCA+ mCRPC (HR, 0.53; 95% CI, 0.36-0.79; P = .001).⁴ These data led to the FDA-approval of the regimen in this setting.

“The final analysis of MAGNITUDE supports the positive benefit-risk profile of first-line niraparib with abiraterone acetate plus prednisone, establishing niraparib with abiraterone acetate plus prednisone as a new standard of care for patients with BRCA+ mCRPC,” said presenting author Kim Nguyen N. Chi, MD, FRCPC, a professor in the department of medicine at the University of British Columbia in Vancouver, Canada.

References

1. Niraparib (NIRA) with abiraterone acetate plus prednisone (AAP) as first-line (1L) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Three-year update and final analysis (FA) of MAGNITUDE. Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract LBA85

2.Chi KN, Sandhu S, Smith MR, et al. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. Published online July 1, 2023. Accessed October 21, 2023. doi: 10.1016/j.annonc.2023.06.009

3. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. 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). Last updated October 11, 2023. Accessed October 20, 2023. https://clinicaltrials.gov/study/NCT03748641

4. 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. Presented at the 2022 ASCO Genitourinary Cancers Symposium. February 17-19, 2022. San Francisco, California. Abstract 12