MAGNITUDE updates in Asian cohort boost NIRA-AAP benefit in BRCA+ mCRPC

In the second interim analysis of the Asian cohort from the phase III MAGNITUDE study, a combination regimen comprising niraparib and abiraterone acetate plus prednisone (NIRA-AAP) improved clinical outcomes in patients with BRCA+ metastatic castration-resistant prostate cancer (mCRPC).

“[In this analysis, the] improvement in radiographic progression-free survival (rPFS) by blinded independent central review with NIRA-AAP compared with placebo-AAP was confirmed, with a 71-percent reduction in the risk of progression or death,” said Dr Marniza Saad from the University Malaya Medical Centre, Kuala Lumpur, Malaysia, during her presentation at ESMO Asia 2023.

The hazard ratio (HR) was 0.29 (95 percent confidence interval [CI], 0.11–0.77; p=0.0084). Median rPFS was longer with NIRA-AAP than with placebo-AAP (22.0 vs 8.3 months). [ESMO Asia 2023, abstract 258MO]

There were also clinically relevant delays in time to symptomatic progression (median not reached [NR] vs 28.9 months; HR, 0.51, 95 percent CI, 0.12–2.11; p=0.3449), time to cytotoxic chemotherapy (median NR vs 16.9 months; HR, 0.08, 95 percent CI, 0.01–0.64; p=0.0024), and time to prostate specific antigen progression (median NR vs 6.5 months; HR, 0.30, 95 percent CI, 0.12–0.77; p=0.0084) in the niraparib vs the placebo arm.

Data on overall survival (OS) were still immature at the time of the second interim analysis and medians were not reached in either arm (HR, 0.86; 95 percent CI, 0.27–2.71; p=0.7941). The 24-month OS was 66.9 months with NIRA-AAP and 58.6 months with placebo-AAP.

Compared with the placebo arm, the niraparib arm had higher rates of drug-related treatment-emergent adverse events (TEAEs; 71 percent vs 55 percent), grade 3/4 TEAEs (71 percent vs 38 percent), and serious AEs (46 percent vs 33 percent). The most common grade 3/4 TEAE tied to NIRA-AAP was anaemia (43 percent); with placebo-AAP, the corresponding rate was 2 percent.

The safety findings aligned with those reported for the global homologous recombination repair-positive (HRR+) cohort, and there were no new safety signals identified, noted Saad.

Poor outcomes

“Patients with mCRPC and HRR gene alterations – especially BRCA alterations – have poor outcomes. Niraparib is a potent PARP 1/2 inhibitor that has shown efficacy in heavily pretreated patients with mCRPC and HRR gene alterations,” Saad said. [J Clin Oncol 2023;41:3339-3351; Lancet Oncol 2022;23:362-373]

In the primary rPFS analysis of MAGNITUDE, NIRA-AAP conferred significant rPFS improvement in patients with HRR+ mCRPC as opposed to placebo-AAP. The second interim analysis of the overall population confirmed the benefit of the combination regimen in patients with BRCA+ mCRPC.

The current subgroup analysis included Asian patients with BRCA+ mCRPC enrolled at study sites in China, Korea, Malaysia, and Taiwan. Of the 423 patients from the global HRR+ cohort, 68 were Asian (median age 71 years). Thirty-six patients from the Asian subgroup were BRCA+, 17 of whom were on NIRA-AAP. Participants were randomized 1:1 to receive either NIRA-AAP or placebo-AAP daily. Niraparib was given at a dose of 200 mg.

“[Taken together, this] longer follow-up of the Asian subgroup confirms the initial observations of the benefit of NIRA-AAP [as first-line treatment] in BRCA+ mCRPC patients, which is consistent with the overall MAGNITUDE study results,” Saad concluded, adding that they will continue to monitor the OS data.