Journal: Nature medicine
The AMPLITUDE trial investigated the efficacy of adding niraparib, a PARP inhibitor, to abiraterone acetate and prednisone (AAP) in patients with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations.
Among 696 patients randomized:
- 56% had BRCA1/2 alterations
- 78% had high-volume metastases
The study demonstrated a significant improvement in radiographic progression-free survival (rPFS) with niraparib plus AAP compared to AAP alone, especially in the BRCA subgroup:
- Median rPFS not reached vs. 26 months
- Hazard Ratio (HR) = 0.52; P < 0.0001
- Overall intention-to-treat population: HR = 0.63; P = 0.0001
Overall survival data are immature but show a trend favoring niraparib.
Grade 3/4 adverse events were more frequent with niraparib (75% vs. 59%), notably:
- Anemia (29%)
- Hypertension (27%)
- Higher blood transfusion rates
This combination offers a clinically meaningful benefit for mCSPC patients with HRR alterations.