A phase III trial has shown that adding niraparib to standard prostate cancer therapy significantly delays disease progression in men with specific DNA repair gene mutations. The AMPLITUDE study, involving 696 men across 32 countries, reported a 37% reduced risk of cancer growth overall and 48% in BRCA-mutated cases. This marks a step toward precision medicine for advanced prostate cancer.
The AMPLITUDE trial, led by Professor Gerhardt Attard of the UCL Cancer Institute and published in Nature Medicine, tested niraparib—a PARP inhibitor—combined with abiraterone acetate and prednisone (AAP), the standard treatment for advanced prostate cancer. The study targeted men with metastatic castration-sensitive prostate cancer and mutations in homologous recombination repair (HRR) genes, such as BRCA1, BRCA2, CHEK2, and PALB2, which affect about one in four such patients and lead to faster progression.
Conducted as a double-blind trial, 696 participants with a median age of 68 were randomized: half received niraparib plus AAP, and half received AAP with placebo. Over half (55.6%) had BRCA1 or BRCA2 mutations. After a median follow-up of 30.8 months, the combination therapy reduced the risk of disease progression by 37% across all participants and by 48% in those with BRCA mutations. It also doubled the time to symptom worsening, with only 16% of the niraparib group experiencing significant progression compared to 34% in the placebo group. A trend toward improved overall survival was observed, though longer follow-up is needed.
Professor Attard stated: "Although current standard treatments are very effective for the majority of patients with advanced prostate cancer, a small but very significant proportion of patients have limited benefit. We now know that prostate cancers with alterations in HRR genes account for a significant group of patients whose disease recurs quickly and has an aggressive course. By combining with niraparib we can delay the cancer returning and hopefully significantly prolonging life expectancy."
Side effects were more common with niraparib, including anemia (leading to 25% of patients needing transfusions) and high blood pressure, with 14 treatment-related deaths versus 7 in the placebo group. The trial, sponsored by Janssen Research & Development, underscores the value of genomic testing at diagnosis.
Prostate cancer affects 1.5 million men globally each year; in the UK, it causes over 56,000 diagnoses and 12,000 deaths annually. Niraparib is approved in the UK for some cancers but awaits approval for prostate cancer.