Updated data demonstrates improved outcomes from the use of niraparib in combination with abiraterone acetate plus prednisone as a first-line therapy in patients with BRCA-positive metastatic castration-resistant prostate cancer
Drs Eleni Efstathiou and Kim Chi (amongst other authors) today presented updated results from the Phase 3 MAGNITUDE study evaluating the investigational use of niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) with or without specific homologous recombination repair (HRR) gene alterations, including BRCA mutations.
In the second interim analysis (IA2) of the MAGNITUDE study (NCT03748641), the treatment combination of niraparib and AAP, in comparison to placebo and AAP at 26.8 months of median follow-up, demonstrated a statistically significant prolongation in time to symptomatic progression (TSP) and continued consistent improvement of time-to-initiation of cytotoxic chemotherapy (TCC) in the HRR-positive population and a strong improvement in TSP for the BRCA subgroup of the HRR-positive population.
Updated radiographic progression free survival (rPFS) results were consistent with the primary analysis which showed statistically significant benefit in both the HRR-positive population and BRCA subgroup.
Additionally, a trend toward improvement in overall survival (OS) was observed in the BRCA subgroup. No new safety signals were identified. The most common adverse events for niraparib and AAP versus placebo and AAP, regardless of causality, were anemia (50.0 percent vs 22.7 percent, respectively), hypertension (33.0 percent vs 22.3 percent) and constipation (33.0 percent vs 15.6 percent). Patients without HRR gene alterations had no improvement in outcomes from the use of niraparib in combination with AAP.
“Patients with HRR-positive mCRPC, especially those with BRCA mutations, are more likely to experience poor outcomes. Although additional follow-up for overall survival continues, it is encouraging to see a trend toward improvement in overall survival among patients with BRCA- positive mCRPC who received niraparib and AAP as compared to placebo and AAP,” said Kim Chi, M.D., Medical Oncologist at BC Cancer - Vancouver and principal investigator of the MAGNITUDE study.
“Taken together, these data continue to support the potential use of niraparib in combination with AAP in patients with mCRPC and BRCA mutations.”
Notably, in the BRCA subgroup (8.1 months additional follow-up at IA2), rPFS by central review demonstrated a consistent and clinically meaningful treatment effect favoring niraparib and AAP, with a median rPFS of 19.5 months at IA2 compared with 10.9 months for placebo and AAP (hazard ratio [HR], 0.55 (95 percent confidence interval [CI], 0.39-0.78).1,2 For patients with BRCA-positive mCRPC, preplanned sensitivity analysis evaluating rPFS by investigator review also showed benefit for niraparib and AAP (HR, 0.46 [95 percent CI, 0.32- 0.67]).
Further, results of the IA2 indicate that patients with BRCA mutations treated with niraparib and AAP experienced a trend towards delayed time to worst pain intensity (HR, 0.70 [95 percent CI, 0.44-1.12]) and pain interference (HR, 0.67 [95 percent CI, 0.40-1.12]) compared with placebo and AAP.
In April 2022, Janssen submitted a marketing authorisation application to the European Medicines Agency seeking approval for niraparib in combination with abiraterone acetate in the form of a dual action tablet (DAT), plus prednisone or prednisolone, based on data from the MAGNITUDE study. Marketing authorisation applications are under review across a number of countries globally.