A recent Phase III study titled AMPLITUDE, led by researchers at UCL, demonstrates that adding the PARP inhibitor niraparib to the standard regimen of abiraterone acetate and prednisone (AAP) significantly delays disease progression in men whose advanced prostate cancer harbours homologous recombination repair (HRR) gene mutations.
The trial, published in Nature Medicine, enrolled 696 men from 32 countries with metastatic prostate cancer initiating first‑line therapy. The median age was 68 years. Half of the participants received the experimental combination (niraparib plus AAP), while the remainder were given AAP with placebo. A majority—55.6 %—carried alterations in BRCA1 or BRCA2, key HRR genes.
Patients and treating physicians were unaware of group assignments, ensuring a double‑blind design. Over a median follow‑up of 30.8 months, the results were noteworthy:
- Risk of progression fell by 37 % overall and by 48 % in those with BRCA1/2 mutations.
- Time to symptomatic deterioration was nearly doubled for the niraparib group, reducing notable worsening from 34 % to 16 %.
- A trend toward longer overall survival appeared in the niraparib arm, though a longer observation period is needed for confirmation.
Professor Gerhardt Attard, head of the UCL Cancer Institute, highlighted the importance of genomic testing at diagnosis. “For men whose tumours carry HRR mutations, combining niraparib with standard therapy can postpone disease recurrence and potentially extend life expectancy,” he said.
The combination was generally well tolerated, yet side effects were more frequent. Anemia and hypertension occurred more often in the niraparib arm, with 25 % of patients requiring blood transfusions. Treatment‑related deaths were higher (14 versus 7), though discontinuation rates remained low.
The authors emphasize the need for ongoing research to confirm long‑term survival benefits and to assess the role of advanced imaging and broader genetic testing in guiding treatment.
Globally, roughly 1.5 million men are diagnosed with prostate cancer each year. In the UK, it is the most frequent cancer in men, with over 56 000 new cases and about 12 000 deaths annually.