A drug that prevents DNA reparation could improve the survival of patients with one of the most aggressive prostate cancers

  • The results of the TRITON3 study show that patients with prostate cancer treated with a PARP inhibitor, called Rucaparib, take almost twice as long for the disease to progress than those treated with conventional chemotherapy.
  • This can become a very good therapeutic alternative for patients with prostate tumors with BRCA mutations, currently with a poor prognosis where hormonal treatments do not work.
  • The study, which has been led by the Gustave Roussy Institute and published in the scientific journal New England Journal of Medicine, has had the outstanding collaboration of the medical oncologist and group leader of the research group at the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO), Josep Ma Piulats, and 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).
NP05 - JM Piulats_NEJM - Imatge noti

A work published in the scientific journal New England Journal of Medicine led by the Gustave Roussy Institute, and which has had the outstanding collaboration of the medical oncologist and group leader of the research group of the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO), Josep Ma Piulats, shows that patients with prostate cancer treated with a PARP inhibitor, called Rucaparib, take almost twice as long for the disease to progress than those who are treated with conventional chemotherapy in tumors with mutations BRCA. The study was presented at the American Society of Clinical Oncology (ASCO) Symposium on Genitourinary Cancers held last weekend in 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 in which hormonal treatments do not fully work. This type of patient represents between 8 and 10% of all patients affected by prostate cancer, for this reason, this would be a 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 PARP (poly-ADP-ribose-polymerase) enzyme, 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 has this study been carried out?

 

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

Thus, in this study, from 4,855 patients with BRCA1, BRCA2, and ATM mutations, 270 have been randomized to be treated with a PARP inhibitor called Rucaparib and the rest with a new generation hormone or chemotherapy treatment with Docetaxel. It should be noted that half of the researchers decided to perform the traditional chemotherapy treatment with Docetaxel. “For this reason, 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.

After analyzing the results, it has been observed that patients treated with Rucaparib take almost twice as long for the disease to progress 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 in which hormonal treatments do not fully work. Therefore, this would be a very good therapeutic alternative for this type of patient with BRCA mutations in prostate cancer, which represent between 8 and 10% of all cases in this type of tumor.

For the medical oncologist specializing in prostate cancer at 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 patients with prostate cancer” and adds, “Currently all patients with advanced prostate cancer should be tested for BRCA 1 and 2 mutations since this not only provides prognostic information but also predicts response to treatment against the molecular target.” For Piulats, these results open a better therapeutic alternative than conventional chemotherapy for patients with very aggressive diseases.

 

 

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).

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