A new combination of treatment could significantly delay the evolution of advanced prostate cancer in men with certain genetic mutations, according to an extensive international study coordinated by researchers at University College London (UCL).
A study, published on Tuesday in the magazine Nature Medicineevaluated the efficiency of adding the drug Niraparib – a Parp inhibitor (enzyme involved in DNA repair) – to the standard treatment with abyrateron and prednisone (AAP).
Phase III study, called Amplitudeincluded 696 patients from 32 countries, with an average age of 68. Half of them received the new therapeutic combination, and the others were treated with the standard and placebo scheme, without doctors or patients know what treatment each (double-blind study) is receiving.
The participants had a metastatic prostate cancer, which are in advanced stage, with changes in the genes involved in the repair of an essential type of DNA defects, known as “Repair by homologous recombination” (HRR).
The homologous recombination is a natural process by which the cells repair the DNA ruptures using an identical or very similar copy of the DNA sequence as a model. Basically, the cell “copies” the intact genetic information on the pair chromosome to replace the damaged part. This mechanism is essential for maintaining the stability of the genome and preventing mutations that can lead to diseases, including cancer.
About a quarter of patients with advanced prostate cancer have such mutations, especially in BRCA1, BRCA2, Chek2 or PALB2 genes, which causes a more aggressive form of the disease and a rapid evolution under conventional treatments.
The results of the study showed that the addition of the Niraparib drug to standard therapy reduced the risk of tumor progression by 37% compared to AAP monotherapy, and in patients with BRCA1 or BRCA2 mutations, the risk reduction was 48%.
In addition, the period until the symptoms were aggravated was double for patients treated with the new combination of treatment, and the proportion of those with a significant deterioration of the symptoms decreased from 34% to 16%.
Although the general tendency indicates an increase in survival, the authors point out that a longer tracking is needed to confirm the benefit in life expectancy.
Professor Gerhardt Attard, the study coordinator, explained that patients with HRR mutations are a distinct, weaker therapeutic response to standard treatments.
“The combination of treatment with Niraparib delays the recurrence (relapse) of the disease and, most likely, significantly prolongs the lifespan. The results support genomic testing and the targeted use of therapy where the benefit is maximum,” he said, quoted in a statement.
The treatment was generally well tolerated, but adverse reactions, in particular anemia and hypertension, were more common in patients in the Nirapaib group. About a quarter of them required blood transfusions. The number of deaths related to treatment was slightly higher in the group that received the new treatment combination (14 compared to 7 in the placebo group), but the general treatment rate has remained low.
The authors emphasize that these results open the way for a personalized approach in the treatment of advanced prostate cancer, but an additional evaluation of long -term benefits, and the impact of extended genetic test and new imaging techniques.
Prostate cancer is the most common form of cancer in men. Worldwide, about 1.5 million cases are diagnosed annually, and in the United Kingdom over 56,000 men receive this diagnosis every year, of which about 12,000 lose their lives due to the disease. The results of the study bring a promising perspective for patients who have so far had few effective therapeutic options.
