Reference: August 2025 | Issue 8 | Vol 11 | Page 4
Results from the international phase 3 Amplitude trial, presented at the 2025 American Society of Clinical Oncology Annual Meeting, suggest that adding niraparib to abiraterone acetate plus prednisone (AAP) can help slow tumour growth in metastatic castration-sensitive prostate cancer (mCSPC) with homologous recombination repair (HRR) gene alterations. These data build on findings from the previous Magnitude study, which led to the approval of niraparib with AAP for HRR-altered metastatic castration-resistant prostate cancer (mCRPC).
The AMPLITUDE trial is a randomised, double-blind, placebo-controlled study evaluating the efficacy of a fixed daily tablet of niraparib (200mg) in combination with abiraterone acetate (1000mg) plus prednisone (5mg) and continuous androgen deprivation therapy (ADT) in patients with mCSPC harbouring at least one HRR mutation in one of the following genes: BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B, and RAD54L.
The trial enrolled 696 patients with mCSPC with either germline or somatic HRR gene alterations. The median age of patients in the study was 68 years. The patients had received no more than six months of treatment with ADT. Eligible patients could have also received six or fewer cycles of docetaxel and/or treatment with AAP for 45 days or fewer if their metastatic cancer had spread outside the lymph nodes.
Participants were randomly assigned to receive either niraparib with AAP (n=348) or AAP with placebo (n=348). More than half (55.6 per cent) had alterations in the BRCA1 or BRCA2 genes and most of the patients had tumours with aggressive features.
At a median follow-up of just over 2.5 years (30.8 months), the researchers found that niraparib was associated with significantly improved radiographic progression-free survival (rPFS) compared to placebo. In patients who received niraparib, the median rPFS was not met, while patients who received placebo had a median rPFS of 29.5 months.
Overall, niraparib reduced the risk of cancer growth by 37 per cent compared to AAP alone in all patients and by 48 per cent in the subgroup of patients with BRCA1 or BRCA2 mutations. Time to worsening of symptoms was longer for patients who received niraparib compared to those who received placebo.
A trend toward improved overall survival was observed in the niraparib group but these data were still immature, as they did not yet meet the criteria for statistical significance.
Serious side effects were more common in the niraparib group. More than 75 per cent of patients experienced serious or life-threatening side effects compared to 58.9 per cent in the placebo group. The most common serious side effects were anaemia and hypertension.
“Metastatic castration-sensitive prostate cancer is a heterogeneous disease with diverse responses to therapies. Although a combination of androgen receptor pathway inhibitors has improved survival in patients with this diagnosis, certain genomic alterations, such as those in the HRR pathway, confer poor prognosis. Therefore, there is still a need for treatments that are tailored to patients whose tumours harbour HRR alterations,” said lead study author Gerhardt Attard from the Cancer Institute at University College London, UK.
Reference
Attard G, Agarwal N, Graff J, et al. Phase 3 AMPLITUDE trial: Niraparib (NIRA) and abiraterone acetate plus prednisone (AAP) for metastatic castration-sensitive prostate cancer (mCSPC) patients (pts) with alterations in homologous recombination repair (HRR) genes. Abstract #LBA5006. American Society of Clinical Oncology Annual Meeting. May 30-June 3, 2025. Chicago, US.
