MAGNITUDE Final Analysis: Niraparib Plus Abiraterone Acetate, Prednisone Boosts OS, Improves TCC

At the European Society for Medical Oncology Congress 2023, Dr. Kim Nguyen N. Chi, of the Vancouver Coastal Health Research Institute, presented a 3-year update and final analysis of the MAGNITUDE trial on the use of niraparib and abiraterone acetate plus prednisone (AAP) as a first-line (1L) therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations.

The MAGNITUDE study began in 2019 and involved the largest population of 1L BRCA-mutated (BRCA+) patients. The primary end point was radiographic progression-free survival, and secondary end points included time to cytotoxic chemotherapy (TCC), time to symptomatic progression (TSP), and overall survival (OS).

A total of 423 eligible patients with HRR+ mCRPC were randomized 1:1 to receive either niraparib with AAP (212 patients) or placebo with AAP (211 patients) as 1L therapy. Upon final analysis, the secondary end points of OS and TCC were formally assessed, along with TSP, patient-reported outcomes (PROs), and safety.

A total of 225 BRCA+ patients were evaluated, with 113 patients receiving niraparib with AAP. The median follow-up was 35.9 months. Subsequent life-prolonging therapy was administered to 70% of patients in the niraparib-with-AAP arm and 86% of patients in the placebo-with-AAP arm.

The niraparib-with-AAP arm saw a higher OS benefit according to a prespecified multivariate analysis adjusted for baseline imbalances. Continued improvement in TSP and a clinically meaningful improvement in TCC were also observed in the same arm, along with time to worst pain progression and time to pain interference progression.

No new safety signals were observed with additional treatment exposure. Pulmonary embolism occurred in 4.7% of patients in the niraparib-with-AAP arm and 1.4% of patients in the placebo-with-AAP arm. No cases of myelodysplastic syndromes or acute myeloid leukemia were reported in the niraparib-with-AAP arm.

Overall, OS favored niraparib with AAP for patients with BRCA+ mCRPC. Niraparib with AAP also led to improvements in TSP, TCC, and PROs, and a positive benefit-risk profile supports the combination as a new 1L standard of care for patients with BRCA+ mCRPC.