Drug that blocks DNA repair could improve survival for patients with one of the most aggressive prostate cancers

A work published in the scientific magazine 'New England Journal of Medicine' led by the Gustave Roussy Institute, and which has had the outstanding collaboration of the medical oncologist of the Catalan Institute of Oncology (ICO) and the Bellvitge Biomedical Research Institute (IDIBELL), Josep Ma Piulats, shows that patients with prostate cancer treated with a PARP inhibitor, called Rucaparib, take almost twice as long to progress the disease than those treated with chemotherapy conventional in tumors with BRCA mutations. The study was presented at the Genitourinary Cancer Symposium of the American Society of Clinical Oncology (ASCO) held last weekend in the city of San Francisco (USA).

These results are important because prostate tumors with BRCA mutations are a subgroup, within this type of tumor, with a poor prognosis where hormonal treatments do not quite work. If we consider that this type of patient represents between 8 and 10% of all patients affected by prostate cancer, this would be a very therapeutic alternative in this group of patients with a worse prognosis.

What is a PARP inhibitor?Inhibitors are a family of drugs that prevent the action of the enzyme PARP (poly -(ADP-ribose)-polymerase), which helps repair DNA damage. When cancer cells have damage to their DNA, their viability is compromised and thanks to this enzyme, they can repair it. If a drug prevents the action of the enzyme, this repair is prevented and can lead to the destruction of the cell.

How was this study conducted?
The TRITON3 study is a Phase III clinical trial in patients with castration-resistant prostate cancer who have previously received next-generation hormonal agents. In this type of situation, the standard treatment is chemotherapy with Docetaxel which is very toxic and which, in this type of patient pre-treated with new generation hormones, is not very effective.

So in this study, of a total of 4,855 patients with BRCA1, BRCA2 and ATM mutations, 270 were randomized to be treated with a PARP inhibitor called Rucaparib and the rest with a new generation hormone or a treatment of Chemotherapy with Docetaxel. It should be noted that half of the researchers decided to do the traditional chemotherapy treatment with Docetaxel."It is for this reason that the results of this study are important since it directly compares the inhibitor against conventional chemotherapy treatment" says Josep Ma Piulats, second author of the study.

Once the results were analyzed, it was observed that patients treated with Rucaparib take almost twice as long to progress the disease compared to standard treatment (from 6 months to 11 months). These results are important because prostate tumors with BRCA mutations are a subgroup, within this type of tumor, with a poor prognosis where hormonal treatments do not quite work. Therefore, this would be a very good therapeutic alternative for this type of BRCA mutated prostate cancer patient, who represent between 8 and 10% of all cases in this type of tumor.

By the medical oncologist specialized in prostate cancer from the Catalan Institute of Oncology-IDIBELL and second author of the study, Josep Ma Piulats,"these results confirm the entry into the new era of personalized medicine for prostate cancer patients" and adds "currently all patients with advanced prostate cancer should be tested for BRCA 1 and 2 mutations since this, not only it gives prognostic information, rather predictive of response to a treatment against the molecular target" . For Piulats, these results open up a better therapeutic alternative than conventional chemotherapy for a group of patients with very aggressive disease.