The AMPLITUDE phase 3 trial demonstrated that adding niraparib to standard hormone therapy significantly extends time to cancer progression in men with metastatic prostate cancer carrying DNA repair gene mutations. Among 696 patients with homologous recombination repair defects, those receiving niraparib plus abiraterone showed a 37% reduction in progression risk compared to standard treatment alone, with particularly striking benefits in the BRCA1/2 subgroup where median progression-free survival was not reached versus 26 months for controls.
This represents a meaningful advance in precision oncology for prostate cancer, as it demonstrates early intervention with PARP inhibitors can be more effective than waiting for hormone resistance to develop—the current standard approach. The strategy capitalizes on synthetic lethality, where cancer cells with existing DNA repair defects become critically vulnerable when PARP enzymes are also blocked. However, the 56% prevalence of BRCA mutations in this cohort suggests careful patient selection was employed, potentially limiting real-world applicability. While overall survival data remain preliminary, the magnitude of benefit particularly in BRCA carriers could establish this combination as a new standard for this genomically defined subset of prostate cancer patients.
