A new drug combination could significantly delay the progression of a life-threatening form of prostate cancer in men with certain genetic mutations, according to the results of a large international study led by UCL researchers.
The Phase III AMPLITUDE study, published in Nature Medicine, tested the addition of niraparib, a targeted cancer drug known as a PARP inhibitor 1, to standard treatment with abiraterone acetate and prednisone (AAP). 2
The study focused on patients diagnosed with advanced prostate cancer that had spread to other parts of the body, who were starting their first treatment, and who also had changes in genes involved in a key type of DNA repair, known as homologous recombination repair (HRR).
These genes help repair damaged DNA. When they are faulty, cancer cells can grow and spread more aggressively. Approximately one in four people with advanced prostate cancer at this stage have changes in HRR genes such as BRCA1, BRCA2, CHEK2 and PALB2.
The standard treatment for advanced prostate cancer currently consists of AAP (or similar drugs, with about one in five patients offered chemotherapy with docetaxel), but these mutations make the cancer more aggressive, and therefore the disease often progresses much faster on standard treatment and life expectancy is shorter.
Led by Professor Gerhardt Attard from the UCL Cancer Institute, 696 men from 32 countries, with an average age of 68, participated in the study. Half of the men received the new combination therapy (niraparib plus APP), and the other half received standard treatment with a placebo. More than half (55.6%) of all patients had changes in the BRCA1 or BRCA2 genes.
The study was double-blind, meaning neither patients nor doctors knew which treatment was being administered.
Key findings
With a median follow-up of just over two and a half years (30.8 months), researchers found:
- Overall, niraparib reduced the risk of cancer growth by 37% compared to AAP alone in all patients, and by 48% in the subgroup of patients with BRCA1 or BRCA2 mutations.
- The time to symptom progression was twice as long for patients receiving niraparib compared to those receiving a placebo. This reduced the number of patients experiencing a noticeable worsening of symptoms from 34% to 16%.
- Researchers observed a trend toward improved overall survival in the niraparib group. However, longer follow-up is needed to confirm that treatment with niraparib improves life expectancy in this patient group.
Professor Attard said: “Although current standard treatments are very effective for the majority of patients with advanced prostate cancer, only a few, but very large, patients benefit limitedly. We now know that prostate cancer with changes in HRR genes represents a significant group of patients whose disease recurs quickly and has an aggressive course. By combining it with niraparib, we can delay the return of cancer and hopefully significantly extend life expectancy.”
DOI: https://doi.org/10.1038/s41591-025-03961-8
