Journal Article

PHASE 3 MAGNITUDE STUDY: RESULTS FROM SECOND INTERIM ANALYSIS OF NIRAPARIB WITH ABIRATERONE ACETATE AND PREDNISONE AS FIRST-LINE THERAPY IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WITH AND WITHOUT HRR GENE ALTERATIONS

Small, Eric, Guckert, Mary, Rathkopf, Dana E, Chi, Kim N

2023

Overview

In the primary analysis of the phase-3 MAGNITUDE study, Niraparib with abiraterone acetate and prednisone (NIRA+AAP) demonstrated significant improvement in clinical outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene-alterations including improvement in radiographic progression free survival (rPFS). This secondary interim analysis (IA2) of the MAGNITUDE study reports the results of secondary endpoints and patient-reported outcomes (PROs). At the prespecified IA2 of the eligible patients (N=423) with mCRPC and HRR gene alterations, secondary endpoints (time to cytotoxic chemotherapy [TCC], time to symptomatic progression [TSP], and overall survival [OS]) were formally assessed and the primary rPFS endpoint and PROs including pain intensity were updated in the HRR alterations (HRR+) cohort, with sensitivity analysis performed for the subgroup of patients with breast cancer gene (BRCA) alterations. Patients were randomized (1:1) to receive NIRA+AAP (n=2i2) or placebo (PBO)+AAP (n=211). In the HRR+ cohort, the revised descriptive rPFS results at IA2 (cutoff: 17 June 2022) were consistent with the primary analysis. NIRA+AAP extended median rPFS to 19.5 months versus 10.9 months with PBO+AAP in the BRCA subgroup. NIRA+AAP led to statistically significant benefit in TSP in the HRR+ cohort with consistent benefit in the BRCA subgroup. In both the HRR+ cohort and the BRCA subgroup, NIRA+AAP showed continued consistent improvement in TCC. In the BRCA subgroup, NIRA+AAP showed a trend towards improved OS in the primary stratified analysis and the multivariate analysis (MVA), accounting for imbalances in key baseline characteristics (Table 1). NIRA+AAP experienced delayed time to worst pain intensity (HR:0.70; 95% CI, 0.44, 1.12; nominal P=0.1338) and pain interference (HR:0.67; 95% CI, 0.40, 1.12; nominal P=0.1275) versus PBO+AAP in BRCA subgroup (Figure). No new safety signals were observed and the safety profile at IA2 was consistent with that of the primary analysis (Table 2). The updated rPFS results at IA2 were consistent with the primary analysis. A statistically significant and meaningful clinical benefit in TSP and meaningful clinical benefit in TCC were observed after 26.8 months of median follow-up. A trend towards improvement in OS was observed in the BRCA subset. A delayed time to worst pain intensity and pain interference was reported. These data continue to support the use of NIRA+AAP in patients with mCRPC and BRCA alterations or select other HRR gene alterations.

• Publisher: Oncology Nursing Society
• Subject: Breast cancer / Chemotherapy / Metastasis / Oncology / Pain / Prostate cancer