Key Takeaways
- First PARP Combo Success in mCSPC with HRR Mutations: Niraparib plus abiraterone acetate and prednisone is the first PARP inhibitor combination to show statistically significant clinical benefit in metastatic castration-sensitive prostate cancer (mCSPC) patients with HRR alterations, including BRCA.
- Strong Efficacy in BRCA-Positive Prostate Cancer: The AMPLITUDE trial demonstrated a 48% reduction in radiographic progression or death and a 56% delay in symptomatic progression among BRCA-altered mCSPC patients receiving the niraparib combination.
- New Hope for Aggressive Prostate Cancer Subtypes: Despite higher rates of anemia and hypertension, the combination’s tolerability and improved outcomes support earlier use in HRR-altered and BRCA-positive mCSPC, addressing a major unmet need in high-risk populations.
Results from the Phase III AMPLITUDE trial show that Johnson & Johnson’s (J&J) combination of niraparib plus abiraterone acetate and prednisone (AAP) is the first PARP inhibitor combination to demonstrate success in treating patients with metastatic castration-sensitive prostate cancer (mCSPC) who have homologous recombination repair (HRR) genetic alterations, including BRCA mutations. According to the company, the niraparib combination demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) and time to symptomatic progression.1
Can a PARP Inhibitor Combination Change the Standard of Care in HRR-Altered mCSPC?
"Approximately 25% of patients with mCSPC have HRR alterations, with about half being BRC,” said Gerhardt Attard, MD, PhD, FRCP, John Black Charitable Foundation chair of medical oncology, University College London Cancer Institute, research department, oncology, presenting author, in a press release. “These patients typically experience faster disease progression and poorer outcomes. The AMPLITUDE trial is the first to show that combining a PARP inhibitor with an androgen receptor pathway inhibitor both delays disease progression and postpones the onset of symptoms in HRR-altered mCSPC, supporting this combination as a new treatment option for these patients."
AMPLITUDE Trial Design and Primary Endpoint
- The ongoing randomized, double-blind, placebo-controlled, international AMPLITUDE trial is evaluating the efficacy and safety of niraparib and AAP in a dual-action tablet formulation, administered with prednisone and androgen deprivation therapy (ADT), versus oral placebo and AAP plus ADT in 696 patients.
- The trial’s primary endpoint is rPFS.
Efficacy Outcomes: BRCA and Broader HRR Population
- Among patients with BRCA alterations, the combination reduced the risk of radiographic progression or death by 48% and delayed symptom progression by 56%.
- In the overall HRR-altered population, the risk of progression or death was reduced by 37%, and symptom progression was delayed by 50%.
- Median rPFS was not reached for patients treated with the niraparib combination, compared to 29.5 months in the placebo group.
Safety Profile and Adverse Events
- Grade 3 or grade 4 adverse events (AEs) were more common in the niraparib combination group at 75% compared to 59% in the placebo cohort, with anemia and hypertension being the most frequently reported AEs.
- Treatment discontinuation rates remained relatively low at 14.7% in the niraparib group versus 10.3% in the placebo group.
CAPTURE Study Supports Need for Targeted Therapies
Complimentary data from the CAPTURE trial, which was presented at the 2025 American Society of Clinical Oncology Annual Meeting, reinforced the poor prognosis associated with HRR and BRCA alterations, even in the presence of existing androgen receptor pathway inhibitor, underscoring a substantial unmet need in this patient population.1
Prostate Cancer Incidence Remains High Among Older Men
According to the American Cancer Society, one in eight men will be diagnosed with prostate cancer during their lifetime. Six out of every ten cases occur in men over 65 years of age, with a median age of diagnosis at 67 years. Prostate cancer is rare in men under 40 years of age. Notably, the risk is significantly higher among African American men and Caribbean men of African ancestry.2
"Our aim with the AMPLITUDE study was to determine how long patients could live without their cancer worsening. What we found is that the combination of niraparib, abiraterone acetate, and prednisone is achieving just that, with the goal of offering patients precious quality time before the disease enters a more resistant phase," said Charles Drake, MD, PhD, FAAP, VP, prostate cancer and immunotherapy disease area leader, Johnson & Johnson Innovative Medicine, in the press release. "This breakthrough highlights the need for early initiation of personalized treatment strategies for patients with mCSPC and HRR alterations, particularly BRCA, who typically face more aggressive disease."
References
1. Johnson & Johnson leads with first PARP inhibitor combo to improve efficacy in patients with HRR-altered mCSPC. PR Newswire. June 3, 2025. Accessed June 4, 2025. https://prnmedia.prnewswire.com/news-releases/johnson--johnson-leads-with-first-parp-inhibitor-combo-to-improve-efficacy-in-patients-with-hrr-altered-mcspc-302471320.html
2. Key Statistics for Prostate Cancer. American Cancer Society. Accessed June 4, 2025. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
