Niraparib (NIRA) with abiraterone acetate and prednisone (AAP) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Second interim analysis (IA2) of MAGNITUDE.
Eleni Efstathiou, Matthew R. Smith, Shahneen Sandhu, Gerhardt Attard, Marniza Saad, David Olmos, Elena Castro, Guilhem Roubaud, Andrea Juliana Gomes, Eric J. Small, Dana E. Rathkopf, Howard Gurney, Wonho Jung, Gary Mason, Peter Francis, George Wang, Daphne Wu, Brooke Diorio, Angela Mennicke Lopez- Gitlitz, Kim N.
Abstract
170 Background: In the primary analysis of the phase 3 MAGNITUDE study, NIRA/AAP significantly improved outcomes in pts with mCRPC and HRR gene alterations. Here, we report results from IA2 of secondary endpoints in MAGNITUDE. Methods: 423 eligible pts with mCRPC and HRR alterations (HRR+ cohort) were randomized 1:1 to receive NIRA/AAP (n = 212) or placebo (PBO)/AAP (n = 211). At the prespecified IA2, secondary endpoints (time to cytotoxic chemotherapy [TCC], time to symptomatic progression [TSP], overall survival [OS]) were formally assessed and the primary rPFS endpoint was updated in the HRR+ cohort, with sensitivity analysis performed for the subgroup of pts with BRCA alterations. Results: Updated descriptive rPFS results at IA2 (cutoff: June 17, 2022) were consistent with the primary analysis in the HRR+ cohort. In the BRCA subgroup, NIRA/AAP extended median rPFS to 19.5 mos vs 10.9 mos with PBO/AAP. NIRA/AAP led to statistically significant benefit in TSP in the HRR+ cohort with consistent benefit in the BRCA subgroup. Continued consistent improvement of TCC was seen with NIRA/AAP in the HRR+ cohort and in the BRCA subgroup. There was a trend towards improved OS with NIRA/AAP in the BRCA subgroup in the primary stratified analysis and the multivariate analysis (MVA), accounting for imbalances in key baseline characteristics. BRCA pts treated with 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) compared to PBO/AAP. The safety profile at IA2 was consistent with that of the primary analysis, with no new safety signals observed. Conclusions: With 26.8 months of median follow-up, there was a statistically significant and meaningful clinical benefit in TSP and meaningful clinical benefit in TCC. Additionally, updated rPFS results from MAGNITUDE IA2 were consistent with the primary analysis; OS benefit was not conclusive due to immaturity and will be followed through to final analysis. Taken together, these data continue to support the use of NIRA/AAP in pts with mCRPC and BRCA alterations or select other HRR gene alterations. Clinical trial information: NCT03748641 . [Table: see text]