Dr Rathkopf on Niraparib Plus Abiraterone Acetate and Prednisone in HRR+ mCSPC

“This is an important study for this patient population. This is a patient population [that] tends to have worse prognosis due to their HRR alteration status."

Dana E. Rathkopf, MD, a genitourinary medical oncologist and chair of the Research Council at Memorial Sloan Kettering Cancer Center, discussed the clinical significance of findings from the phase 3 AMPLITUDE trial (NCT04497844) of niraparib plus abiraterone acetate (Zytiga) and prednisone for patients with homologous recombination repair (HRR) gene–mutated metastatic castration-sensitive prostate cancer (mCSPC).

Findings from AMPLITUDE presented during the 2025 ASCO Annual Meeting revealed that patients with HRR-mutated mCSPC who received niraparib plus abiraterone acetate and prednisone (n = 348) achieved a median radiographic progression-free survival (rPFS) that was not evaluable compared with 29.5 months among patients who received placebo with abiraterone acetate and prednisone (n = 348; HR, 0.63; 95% CI, 0.49-0.80; P = .0001); these findings met the primary end point of the trial. Moreover, the addition of niraparib to abiraterone acetate and prednisone yielded a significant benefit in terms of time to symptomatic progression (TTSP; HR, 0.50; 95% CI, 0.36-0.69; P < .0001).

Regarding safety, patients in the investigational arm experienced grade 3 or 4 treatment-emergent adverse effects (TEAEs) at a rate of 75%; 56% of these were treatment related. TEAEs leading to treatment discontinuation (15%), dose reduction (22%), and death (4%) were all reported.

These findings were significant for patients with HRR-mutated mCSPC because these patients tend to have a worsened prognosis due to their HRR mutational status, Rathkopf said. The option for a targeted regimen that includes the PARP inhibitor niraparib is key due to the improvement in rPFS and TTSP that it offers over standard of care approaches, she emphasized. Additionally, the regimen was well tolerated, she said. This approach offers patients an opportunity to do maximize their outcomes, Rathkopf concluded.