ProBio Trial: Niraparib Plus Abiraterone Shows Greater Clinical Benefit in BRCA-Mutated mCRPC

New findings from the randomized phase 3  ProBio platform trial suggest that niraparib combined with abiraterone and prednisone may extend clinical benefit in patients with metastatic castration-resistant prostate cancer (mCRPC) carrying homologous recombination repair (HRR) gene alterations, particularly BRCA1/2 mutations. However, no overall survival advantage was demonstrated.

The analysis included 99 patients, with 54 receiving niraparib plus abiraterone and prednisone and 45 receiving standard-of-care treatment. ProBio uses circulating tumor DNA (ctDNA) profiling to identify genetic alterations and guide treatment randomization. Initially, patients were eligible regardless of HRR status, but enrollment into this comparison was subsequently restricted to those with HRR alterations.

The primary endpoint was time to no longer clinically benefiting (NLCB), assessed according to PCWG3 criteria. Among HRR-positive patients, median time to NLCB was 19.1 months with the combination versus 14.4 months with standard care.

The strongest numerical difference emerged in patients with BRCA1/2 alterations, with median time to NLCB of 15.3 versus 7.0 months, respectively. In contrast, patients with TP53 mutations showed no meaningful difference between treatment groups.

Importantly, overall survival in the HRD-positive population was similar between groups, with median survival of 24.4 months for niraparib plus abiraterone and 24.9 months for standard care.

These findings are consistent with the broader evidence from MAGNITUDE suggesting that the benefit of PARP inhibition is greatest in BRCA-mutated prostate cancer.

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