Dr Saraiya on the AMPLITUDE Trial in mCSPC
Biren Saraiya, MD, provides background on the phase 3 AMPLITUDE study evaluating niraparib plus abiraterone acetate in metastatic castration-sensitive prostate cancer.
The AMPLITUDE trial (NCT04497844), a double-blind, placebo-controlled study, investigated the efficacy and safety of niraparib (Zejula) in combination with abiraterone acetate (Zytiga) plus prednisone (AAP) for patients with HRR-altered metastatic castration-resistant prostate cancer (mCSPC). Here, Biren Saraiya, MD, medical oncologist at Rutgers Cancer Institute, provides background on the study.
Niraparib is a highly selective and potent PARP inhibitor, previously showing improved radiographic progression-free survival (rPFS) with abiraterone acetate plus prednisone in a similar patient population in the MAGNITUDE trial.
Eligible patients with germline or somatic HRR gene alterations (including BRCA1, BRCA2) were randomized 1:1 to receive either a dual-action tablet of niraparib 200 mg plus AAP or placebo plus AAP. Patients had limited prior treatment, including up to 6 months of androgen deprivation therapy and optional prior docetaxel. The primary end point was investigator-assessed rPFS, while secondary end points included time to symptomatic progression (TSP), overall survival (OS), and safety.
A total of 696 patients were enrolled. After a median follow-up of 30.8 months, the trial successfully met its primary end point. Radiographic progression-free survival was significantly longer in the niraparib/AAP arm (median not reached) compared to the AAP arm (29.5 months), with a hazard ratio of 0.63 (P =.0001). This benefit was also observed in the prespecified BRCA1/2 subgroup. Time to symptomatic progression was also significantly improved with niraparib/AAP (HR, 0.50; P <.0001). While a favorable trend in overall survival was noted, statistical significance was not yet reached at this first interim analysis.
Regarding safety, grade 3/4 adverse events were more frequent with niraparib/AAP (75.2%) vs AAP alone (58.9%), predominantly due to anemia and hypertension. However, treatment discontinuations due to adverse events remained low in both groups. The findings suggest that nirarparib/AAP significantly improves rPFS and TSP, and has a favorable effect on OS without new safety concerns, supporting its potential as a new standard of care for patients with HRR-altered mCSPC.
