Dr Attard on Niraparib/Abiraterone Acetate Plus Prednisone in mCRPC With HRR Alterations

“This analysis is immature, but the OS trend is favorable, with a hazard ratio of 0.75 in the BRCA-mutated group and 0.79 in the whole population.”

Gerhardt Attard, MD, PhD, FRCP, professor of oncology at University College London Cancer Institute, discussed the clinical implications of the phase 3 AMPLITUDE trial (NCT04497844), which evaluated the addition of niraparib (Zejula) to abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations.

The trial’s hierarchical statistical design prioritized evaluation in the BRCA1/2-mutated subgroup before assessing the overall HRR-altered population. In both groups, niraparib plus AAP significantly prolonged radiographic progression-free survival (rPFS) compared with AAP alone. Median rPFS was not evaluable in the experimental arm vs 29.5 months with AAP (HR, 0.63; 95% CI, 0.49-0.80; P = .0001), and the benefit was more pronounced in the BRCA1/2-mutated subgroup (HR, 0.52; 95% CI, 0.37-0.72; P < .0001).

Data in terms of key secondary end points also favored the combination. Time to symptomatic progression was reduced by 56% in the BRCA1/2-mutated subgroup (HR, 0.44; 95% CI, 0.29-0.68; P = .0001) and by 50% in the overall population (HR, 0.50; 95% CI, 0.36-0.69; P < .0001). Interim overall survival (OS) analyses, with approximately half the required death events, showed favorable trends (HR, 0.75 in the BRCA1/2-mutated subgroup; HR, 0.79 in the overall population), though interpretation is limited by 36% of patients in the control arm receiving subsequent PARP inhibition.

Attard noted that the safety profile reflected the expected toxicity of niraparib, with grade 3 or 4 adverse events occurring in 75% of patients receiving niraparib plus AAP compared with 59% in the placebo group. No new safety signals were identified, but the higher incidence of toxicities underscores the importance of patient selection and monitoring in clinical practice.

These findings, Attard explained, support niraparib plus AAP as a targeted approach for patients with mCSPC and HRR alterations, particularly those with BRCA1/2 mutations. The regimen offers a significant rPFS advantage and delays symptomatic progression, with OS benefit pending maturation of final data. He emphasized the need to contextualize these results within the evolving treatment landscape and the potential impact of crossover to PARP inhibitors in the control arm when interpreting long-term survival outcomes.