Innovative Drug Combo Shows Promise for Treating Advanced Prostate Cancer

A groundbreaking international trial led by researchers from University College London has revealed that a new combination of drugs could significantly delay the progression of advanced prostate cancer in men with specific genetic mutations. Published in Nature Medicine, the Phase III AMPLITUDE trial investigated the effects of adding niraparib, a PARP inhibitor targeting DNA repair mechanisms, to the standard treatment of abiraterone acetate and prednisone (AAP). The study focused on patients diagnosed with metastatic prostate cancer who carried alterations in homologous recombination repair (HRR) genes, such as BRCA1, BRCA2, CHEK2, and PALB2. Approximately 25% of men with advanced prostate cancer at this stage have these genetic mutations, which make the cancer more aggressive and lead to faster disease progression under conventional therapies. The trial involved 696 men across 32 countries, with a median age of 68. Participants were randomized to receive either the new drug combination or standard treatment with a placebo, in a double-blind setup. Results after a median follow-up of about 31 months showed that niraparib reduced the risk of cancer progression by 37% overall and by 48% in patients with BRCA gene mutations. Patients receiving niraparib experienced a longer duration before symptom worsening, with the time doubled compared to standard therapy. Although a trend towards improved overall survival was observed, longer follow-up is necessary for confirmation. Side effects of the combination treatment were more frequent, notably anemia and high blood pressure, with 25% of patients requiring blood transfusions. Treatment-related deaths were higher in the niraparib group but overall discontinuation rates remained low. Lead researcher Professor Gerhardt Attard emphasized that these findings support widespread genetic testing at diagnosis to tailor treatments for patients most likely to benefit, potentially prolonging life and delaying disease recurrence. The study highlights the importance of integrating targeted therapies like niraparib into prostate cancer management, especially for genetically altered tumors. Further research is ongoing to confirm long-term survival benefits and explore broader genetic profiling and imaging techniques.